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  • 2000-2004  (35)
  • 1950-1954  (2,076)
  • 1880-1889  (2,164)
  • Organic Chemistry  (4,240)
  • Biochemistry and Biotechnology
  • Nuclear reactions
  • pharmacokinetics
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  • 1
    Electronic Resource
    Electronic Resource
    Phase I and pharmacological study of increased dose oral topotecan in combination with intravenous cisplatin (2000)
    Springer
    Annals of oncology 11 (2000), S. 1205-1207 
    Details
    ISSN: 1569-8041
    Keywords: cisplatin ; pharmacokinetics ; phase I ; oral topotecan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008396414915
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  • 2
    Electronic Resource
    Electronic Resource
    A phase I dose escalation study of the matrix metalloproteinase inhibitor BAY 12-9566 administered orally in patients with advanced solid tumours (2000)
    Springer
    Annals of oncology 11 (2000), S. 1579-1584 
    Details
    ISSN: 1569-8041
    Keywords: dosing ; inhibitor ; matrix metalloproteinase ; pharmacokinetics ; solid tumours ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:This phase I study was performed to evaluatethe safety, tolerability, and efficacy of the oral matrixmetalloproteinase inhibitor BAY 12-9566 in patients with advanced solidtumours, and to identify the maximum tolerated dose and dose for use insubsequent studies. Patients and methods:BAY 12-9566 was administered to 29 patientsat doses ranging from 100 mg o.d. to 1600 mg (given either 400 mg q.i.d. or800 mg b.i.d.). Blood samples for pharmacokinetic analyses were drawn on days1–5, day 15 and days 29 and 30. Patients were continued on daily oraltreatment of BAY 12-9566 until a dose limiting toxicity or tumour progressionoccurred. Results:A maximum tolerated dose was not defined because plasmalevels of BAY 12-9566 could not be sufficiently increased, even withescalating doses of drug. Pharmacokinetic analysis suggested that absorptionwas saturable at higher doses. The predominant toxicities related to drug wereasymptomatic reversible effects on platelets and transaminases and mildanemia. There were no significant musculoskeletal toxicities. No objectiveresponses were seen at the doses tested, but stable disease was observed insome patients based on tumour measurements. Conclusions:The recommended dose of BAY 12-9566 for furtherstudies is 800 mg b.i.d. as this dose provides maximal plasma levels that canbe achieved with a convenient dosing schedule for a chronically administeredoral agent
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008347630465
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and bioequivalence of a combined oral formulation of eniluracil, an inactivator of dihydropyrimidine dehydrogenase, and 5-fluorouracil in patients with advanced solid malignancies (2000)
    Springer
    Annals of oncology 11 (2000), S. 1313-1322 
    Details
    ISSN: 1569-8041
    Keywords: 776C85 ; bioequivalence ; dihydropyrimidine dehydrogenase inhibitor ; eniluracil ; 5-fluorouracil ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:This study was performed to evaluate thepharmacokinetics, bioequivalence, and feasibility of a combined oralformulation of 5-flurouracil (5-FU) and eniluracil (Glaxo Wellcome Inc.,Research Triangle Park, North Carolina), an inactivator of dihydropyrimidinedehydrogenase (DPD). The rationale for developing a combined eniluracil/5-FUformulation oral dosing form is to simplify treatment with these agents, whichhas been performed using separate dosing forms, and decrease the probabilityof severe toxicity and/or suboptimal therapeutic results caused byinadvertently high or conversely insufficient 5-FU dosing. Patients and methods:The trial was a randomized, three-waycrossover bioequivalence study of three oral dosing forms of eniluracil/5-FUtablets in adults with solid malignancies. Each period consisted of two daysof treatment and a five- to seven-day washout phase. Eniluracil at a dose of20 mg, which results in maximal DPD inactivation, was administered twice dailyon the first day and in the evening on the second day of each of the threetreatments. On the morning of the second day, all patients received a totaleniluracil dose of 20 mg orally and a total 5-FU dose of 2 mg orally as eitherseparate tablets (treatment A) or combined eniluracil/5-FU tablets in twodifferent strengths (2 tablets of eniluracil/5-FU at a strength (mg/mg) of10/1 (treatment B) or 8 tablets at a strength of 2.5/0.25 (treatment C)). Thepharmacokinetics of plasma 5-FU, eniluracil, and uracil, and the urinaryexcretion of eniluracil, 5-FU, uracil, and α-fluoro-β-alanine (FBAL),were studied. To determine the bioequivalence of the combined eniluracil/5-FUdosing forms compared to the separate tablets, an analysis of variance onpharmacokinetic parameters reflecting eniluracil and 5-FU exposure wasperformed. Results:Thirty-nine patients with advanced solid malignancies hadcomplete pharmacokinetic studies performed during treatments A, B, and C. Thepharmacokinetics of eniluracil and 5-FU were similar among the three types oftreatment. Both strengths of the combined eniluracil/5-FU dosing form and theseparate dosing forms were bioequivalent. Mean values for terminal half-life,systemic clearance, and apparent volume of distribution for oral 5-FU duringtreatments A/B/C were 5.5/5.6/5.6 hours, 6.6/6.6/6.5 liters/hour, and50.7/51.5/50.0 liters, respectively. The intersubject coefficient of variationfor pharmacokinetic variables reflecting 5-FU exposure and clearance intreatments ranged from 23% to 33%. The urinary excretion ofunchanged 5-FU over 24 hours following treatments A, B, and C averaged52.2%, 56.1%, and 50.8% of the administered dose of 5-FU,respectively. Parameters reflecting DPD inhibition, including plasma uraciland urinary FBAL excretion following treatments A, B, and C were similar.Toxicity was generally mild and similar following all three types oftreatments. Conclusions:The pharmacokinetics of 5-FU and eniluracil weresimilar and met bioequivalence criteria following treatment with the separateoral formulations of 5-FU and eniluracil and two strengths of the combinedformulation. The availability of a combined eniluracil/5-FU oral dosing formwill likely simplify dosing and decrease the probability of severe toxicityor suboptimal therapeutic results caused by an inadvertent 5-FU overdose orinsufficient 5-FU dosing in the case of separate oral formulations, therebyenhancing the overall feasibility and therapeutic index of oral 5-FU therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008379802642
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  • 4
    Electronic Resource
    Electronic Resource
    Clinical and pharmacological phase I study with accelerated titration design of a daily times five schedule of BBR3464, a novel cationic triplatinum complex (2000)
    Springer
    Annals of oncology 11 (2000), S. 977-983 
    Details
    ISSN: 1569-8041
    Keywords: BBR3464 ; phase I ; platinum analog ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives:To define the maximum tolerated dose (MTD), thetoxicity and pharmacokinetic profile of BBR3464, a novel triplatinum complex. Patients and methods:Fourteen patients with advanced solid tumorsnot responsive to previous antitumor treatments received BBR 3464 on a daily× 5 schedule every twenty-eighth day. The drug was given as a one-hourinfusion with pre-and post-treatment hydration (500 ml in one hour) and noantiemetic prophylaxis. The starting dose was 0.03 mg/m2/day. Amodified accelerated titration escalation design was used. Total and freeplatinum (Pt) concentrations in plasma and urine were assessed by ICP-MS ondays 1 and 5 of the first cycle. Results:Dose was escalated four times up to 0.17mg/m2/day. Short-lasting neutropenia and diarrhea of late onsetwere dose-limiting and defined the MTD at 0.12 mg/m2. Nausea andvomiting were rare, neither neuro- nor renal toxic effects were observed.BBR3464 showed a rapid distribution phase of 1 hour and a terminal half-lifeof several days. At 0.17 mg/m2 plasma Cmax and AUC on day 5 werehigher than on day 1, indicating drug accumulation. Approximately 10%of the equivalent dose of BBR3464 (2.2%–13.4%) wasrecovered in a 24-hour urine collection. Conclusions:The higher than expected incidence of neutropenia andGI toxicity might be related to the prolonged half-life and accumulation oftotal and free Pt after daily administrations. Lack of nephrotoxicity and thelow urinary excretion support the use of the drug without hydration. Thesingle intermittent schedule has been selected for clinical development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008302309734
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  • 5
    Electronic Resource
    Electronic Resource
    A phase I–II study of 9-cis retinoic acid and interferon-α2b in patients with advanced renal-cell carcinoma: An NCIC Clinical Trials Group study (2000)
    Springer
    Annals of oncology 11 (2000), S. 1387-1389 
    Details
    ISSN: 1569-8041
    Keywords: interferon-α ; pharmacokinetics ; renal carcinoma ; retinoids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although advanced renal-cell carcinoma (RCC) responds poorly to standardtherapies, phase I–II trials have shown activity for combinations ofinterferon-α2b (IFN) with a retinoid. Alitretinoin (9-cis RA) isan endogenous retinoid with high binding affinity for both RAR and RXRreceptor families. This phase I–II study enrolled 38 patients with RCCin a dose-escalation study of tolerability, pharmacokinetics (PK), andefficacy of twice daily oral 9-cis RA with subcutaneous IFN. Incontrast to studies with similar doses of daily 9-cis RA, PK studiesfound a consistent reduction in 9-cis RA concentrations of about50% after multiple b.i.d. doses of 30 or 50 mg/m2,independent of cotreatment with IFN. In the phase I portion, toxicitiesincluded systemic symptoms typical of IFN and biochemical abnormalitiespreviously associated with retinoids. Two patients experienced dose-limitingtoxicity at 50 mg/m2 b.i.d. of 9-cis RA, thus therecommended phase II dose was 30 mg/m2 b.i.d. One of twenty-sixevaluable patients achieved a durable objective partial remission, andrepeated dosing with this regimen was poorly tolerated. This combination ofretinoid and interferon is not recommended for further study in RCC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026579400806
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  • 6
    Electronic Resource
    Electronic Resource
    Pegylated liposomal doxorubicin in treating a case of advanced hepatocellular carcinoma with severe hepatic dysfunction and pharmacokinetic study (2000)
    Springer
    Annals of oncology 11 (2000), S. 349-354 
    Details
    ISSN: 1569-8041
    Keywords: chemotherapy ; doxorubicin ; hepatocellular carcinoma ; liposome ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There is lack of effective and safe chemotherapy foradvanced hepatocellular carcinoma. Polyethylene glycol-coated (pegylated)liposomal doxorubicin (PLD) has long circulation time and enhanced drugaccumulation in the tumor tissues. It has significant activity in Kaposi'ssarcoma, breast and ovarian cancers and the acute adverse effects of free drugare reduced. Patients and methods:A patient with advanced hepatocellularcarcinoma was treated with PLD and a pharmacokinetic study was performed.Initial serum total and direct bilirubin were 3.6 and 6.8 folds of uppernormal, respectively, and an indocyanine green clearance test at 15 minuteswas 26.3% (normal 〈 15%). Results:Compared to cases with normal liver function, increasedvolume of distribution of doxorubicin correlated with a large amount ofascites (P〈 0.05). The clearance of drug was unexpectedly higherthan in cases with normal liver function (P〈 0.05). According tothe pharmacokinetic studies, the disposition of PLD in this case has not beenretarded even in the presence of severe liver dysfunction. Only minimaltoxicities including grade 2 stomatitis and moderate leukopenia were observed.The tumor had a partial remission and the patient survived nine months afterPLD treatment. Conclusion:PLD could serve as a safe and effective treatment forhepatocellular carcinoma even in the presence of impaired liver function. Itsrole in treating advanced hepatocellular carcinoma is worthy of further study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008394125040
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  • 7
    Electronic Resource
    Electronic Resource
    Pharmacology of Fluorinated Pyrimidines: Eniluracil (2000)
    Springer
    Investigational new drugs 18 (2000), S. 373-381 
    Details
    ISSN: 1573-0646
    Keywords: clinical pharmacology ; dihydropyrimdine dehydrogenase ; eniluracil ; oral 5-FU ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacological inactivation of dihydropyrimidine dehydrogenase (DPD)represents one strategy to improve 5-FU therapy, which historically hasbeen associated with unpredictable pharmacological behavior andtoxicity. This is principally due to high interpatientdifferences in the activity of DPD, the enzyme that mediates theinitial and rate-limiting step in 5-FU catabolism. Byinactivating DPD and suppressing the catabolism of 5-FU,eniluracil has dramatically altered the pharmacological profileof 5-FU. The maximum tolerated dose of oral 5-FU given with oraleniluracil (1.0 to 25 mg/m2) is substantially lower thanconventional 5-FU doses. In the presence of eniluracil,bioavailability of 5-FU has increased to approximately 100%, thehalf-life is prolonged to 4 to 6 hours, and systemic clearanceis reduced 〉 20-fold to values comparable the glomerularfiltration rate (46 to 58 mL/min/m2). Renal excretion(∼ 45% to 75%), instead of DPD-related catabolism, is theprincipal route of elimination of oral 5-FU given witheniluracil. Chronic daily administration of oral 5-FU 1.0mg/m2 twice daily with eniluracil 20 mg twice dailyproduces 5-FU steady-state concentrations (8–38 ng/mL) similarto those achieved with protracted intravenous administration onclinically relevant dose-schedules. On a daily × 5regimen, higher 5-FU AUC values are related to neutropenia,whereas elevated 5-FU AUC and steady-state concentrations arerelated to diarrhea when oral 5-FU is given daily with eniluracilon a chronic schedule. The pharmacokinetic behavior of oraleniluracil is similar to that for oral 5-FU. Administration ofeniluracil 10 to 20 mg twice daily completely inactivates DPDactivity both in peripheral blood mononuclear cells and incolorectal tumor tissue, and prolonged inhibition of DPD afterdiscontinuation of eniluracil treatment has been noted. In thepresence of eniluracil, oral administration of 5-FU is feasibleand variation in 5-FU exposure is reduced, with the anticipationof further reduction in variation as dosing guidelines based onrenal function are formulated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006453500629
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  • 8
    Electronic Resource
    Electronic Resource
    Disposition Kinetics and Urinary Excretion of Pefloxacin after Intravenous Injection in Crossbred Calves (2000)
    Springer
    Veterinary research communications 24 (2000), S. 189-196 
    Details
    ISSN: 1573-7446
    Keywords: cattle ; dosage ; fluoroquinolone ; pefloxacin ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The disposition kinetics and urinary excretion of pefloxacin after a single intravenous administration of 5 mg/kg were investigated in crossbred calves and an appropriate dosage regimen was calculated. At 1 min after injection, the concentration of pefloxacin in the plasma was 18.95±0.892 μg/ml, which declined to 0.13±0.02 μg/ml at 10 h. The pefloxacin was rapidly distributed from the blood to the tissue compartment as shown by the high values for the initial distribution coefficient, α (12.1±1.21 h–1) and the constant for the rate of transfer of drug from the central to the peripheral compartment, K 12 (8.49±0.99 h–1). The elimination half-life and volume of distribution were 2.21±0.111 h and 1.44±0.084 L/kg, respectively. The total body clearance (ClB) and the ratio of the drug present in the peripheral to that in the central compartment (P/C ratio) were 0.454±0.026 L/kg h) and 5.52±0.519, respectively. On the basis of the pharmacokinetic parameters obtained in the present study, an appropriate intravenous dosage regimen for pefloxacin in cattle for most of the bacteria sensitive to it would be 6.4 mg/kg repeated at 12 h intervals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006408415431
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  • 9
    Electronic Resource
    Electronic Resource
    A Survey of the Literature (1995–1999) on the Kinetics of Drugs in Camels (Camelus dromedarius) (2000)
    Springer
    Veterinary research communications 24 (2000), S. 245-260 
    Details
    ISSN: 1573-7446
    Keywords: anthelmintic ; antibiotic ; camel ; chemotherapy ; enzymes ; pharmacokinetics ; xenobiotic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent publications dealing mainly with the kinetics of antiparasitic and antibacterial agents, NSAIDs, and other drugs in camels are briefly reviewed. The kinetic data for most of these drugs indicated that they have longer absorption and elimination half-lives and slower systemic clearance in the camel compared to other animals. This corroborates earlier reports that suggested that the activities of drug-metabolizing enzymes and the capacity to biotransform and eliminate xenobiotics is lower in camels than in other ruminants. There is a clear need to establish basic kinetic data for the camel in order to avoid extrapolation of drug dosage regimens and withdrawal times from data for other animals, as this may result in irrational use of drugs in camels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006498816669
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetic Behaviour of Albendazole Sulphoxide Enantiomers in Male and Female Sheep (2000)
    Springer
    Veterinary research communications 24 (2000), S. 339-348 
    Details
    ISSN: 1573-7446
    Keywords: anthelmintic ; benzimidazole ; chromatography ; enantiomer ; metabolism ; pharmacokinetics ; sex ; sheep
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Benzimidazole anthelmintic drugs are widely used in veterinary practice. Albendazole sulphoxide (ABZSO) is a benzimidazole drug with two enantiomers, as a consequence of a chiral centre in the sulphoxide group. The kinetics of these enantiomers were studied in male and female sheep. Plasma samples were obtained from the animals between 0.5 and 72 h after oral administration of 7.5 mg/kg of a racemic formulation of ABZSO (total-ABZSO). After a liquid–liquid extraction, the samples were analysed by HPLC to determine the concentrations of total-ABZSO and of the sulphone metabolite (ABZSO2). During the chromatographic analysis, the ABZSO peak was collected and reanalysed by an HPLC technique using a Chiral AGP column to quantify the enantiomeric proportion therein. After kinetic analysis, the AUCs obtained for the (+)-ABZSO were 5.8 and 4.0 times higher than those for the (–)-ABZSO in male and female animals, respectively. The mean residence times were 23.4 and 16.1 h for (+)-ABZSO and 22.2 and 17.4 h for (–)-ABZSO for male and female animals, respectively. The only significant difference between the sexes (p〈0.05) was in the T max of the (–)-ABZSO. Comparing both enantiomers within each sex, significant differences were found in all the kinetic parameters. Finally, no kinetic differences were found between sex for total-ABZSO or ABZSO2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006496122684
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  • 11
    Electronic Resource
    Electronic Resource
    Allometric Pharmacokinetic Scaling: Towards the Prediction of Human Oral Pharmacokinetics (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 410-418 
    Details
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To evaluate (1) allometric scaling of systemic clearance (CL)using unbound drug concentration, (2) the potential usage of brainweight (BRW) correction in allometric scaling of both CL and oralclearance (CL/F). Methods. Human clearance was predicted allometrically (CLu = a ·Wbiv) using unbound plasma concentration for eight Parke-Daviscompounds and 29 drugs from literature sources. When the exponent bivwas higher than 0.85, BRW was incorporated into the allometricrelationship (CLu*BRW = a · Wbiv). This approach was also applied tothe prediction of CLu/F for 10 Parke-Davis compounds. Human oralt1/2, Cmax, AUC, and bioavailability were estimated based onallometrically predicted pharmacokinetic (PK) parameters. Results. Human CL and CL/F were more accurately estimated usingunbound drug concentration and the prediction was further improvedwhen BRW was incorporated into the allometric relationship. ForParke-Davis compounds, the predicted human CL and CL/F werewithin 50-200% and 50-220% of the actual values, respectively. Theestimated human oral t1/2, Cmax, and AUC were within 82-220%,56-240%, and 73-190% of the actual values for all 7 compounds,suggesting that human oral PK parameters of those drugs could bereasonably predicted from animal data. Conclusions. Results from the retrospective analysis indicate thatallometric scaling of free concentration could be applied to orallyadministered drugs to gain knowledge of drug disposition in man, and to helpdecision-making at early stages of drug development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007520818956
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  • 12
    Electronic Resource
    Electronic Resource
    In Vivo Absorption Properties of Orally Administered Recombinant Human Interleukin-11 (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 482-485 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; recombinant human interleukin-11 ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007545524408
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  • 13
    Electronic Resource
    Electronic Resource
    New Insights into the Pharmacokinetics and Metabolism of (R,S)-Ifosfamide in Cancer Patients Using a Population Pharmacokinetic-Metabolism Model (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 645-652 
    Details
    ISSN: 1573-904X
    Keywords: (R,S)-Ifosfamide ; R2-, R3-, S2-, S3-DCE-IFF ; iterative-two stage analysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of R- andS-Ifosfamide (IFF), and their respective 2 and 3 N-dechloroethylated (DCE)metabolites (R2-, R3-, S2, S3-DCE-IFF) in cancer patients. Methods. (R,S)-IFF was administered (1.5 g/m2)daily for 5 days in 13 cancer patients. Plasma and urine samples were collectedand analyzed using an enantioselective GC-MS method. An average of 97observations per patient were simultaneously fitted using apharmacokinetic-metabolism (PK-MB) model. A population PK analysis was performedusing an iterative 2-stage method (IT2S). Results. Auto-induction of IFF metabolism was observed over the 5day period. Increases were seen in IFF clearance (R: 4 vs 7 L/h; S: 5vs 10 L/h), and in the formation of DCE (R: 7 vs 9%; S: 14 vs 19%)and active metabolites (4-OHM-IFF; R: 71 vs 77%; S: 67 vs 71%). Anovel finding of this analysis was that the renal excretion of the DCEmetabolites was also induced. Conclusions. This population PK-MB model for (R,S)-IFF may beuseful in the optimization of patient care, and gives new insight intothe metabolism of (R,S)-IFF.
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    URL: http://dx.doi.org/10.1023/A:1007561727948
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  • 14
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and Antitumor Effect of Doxorubicin Carried by Stealth and Remote Loading Proliposome (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 782-787 
    Details
    ISSN: 1573-904X
    Keywords: stealth and remote loading proliposome ; doxorubicin ; pharmacokinetics ; acute toxicity ; anticancer effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of the study was to prepare stealth and remoteloading proliposome (SRP-L) to carry doxorubicin (DXR) and evaluatethe pharmacokinetics, acute toxicity, and anticancer effect of DXRcarried with SRP-L. Methods. SRP-L was transparent solution. When SRP-L was injectedinto 0.9% NaCl aqueous solution containing DXR, liposomes formedand automatically loaded DXR (SRP-L-DXR). The long circulation ofSRP-L-DXR was evaluated using the pharmacokinetics ofSRP-L-DXR, cardiolipin liposomal DXR (CL-DXR) and free DXR (F-DXR).The acute toxicity and anticancer effect of SRP-L-DXR were evaluatedin C57BL/6 mice and murine hystocytoma M5076 tumor model. Results. The average diameter of SRP-L-DXR in pure water was112.9 ± 8.6 (nm) and the encapsulation efficiency of SRP-L-DXRwas 96.5 ± 0.2% in pure water, 95.5 ± 0.1% in 5% glucose and 98.01± 0.6% in 0.9% NaCl. The plasma concentration of SRP-L-DXR wasmuch higher than those of F-DXR and CL-DXR. Compared with thatof F-DXR, the SRP-L-DXR had lower acute toxicity and its anticancereffects depended upon the therapeutic treatment. Conclusions. A novel proliposome (SRP-L) was developed, whichcould automatically load DXR and form SRP-L-DXR with excellentcharacteristics. SRP-L-DXR had lower acute toxicity but was notalways more effective for the treatment of the ascitic M5076 thanF-DXR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007543805947
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  • 15
    Electronic Resource
    Electronic Resource
    Pharmacokinetic-Pharmacodynamic Modelling of Morphine Transport Across the Blood-Brain Barrier as a Cause of the Antinociceptive Effect Delay in Rats—A Microdialysis Study (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1220-1227 
    Details
    ISSN: 1573-904X
    Keywords: morphine ; nociceptive effect ; electrical stimulation vocalisation method ; microdialysis ; retrodialysis by drug ; pharmacokinetics ; pharmacodynamics ; modelling ; blood-brain barrier transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To quantify the contribution of distributional processes across the blood-brain barrier (BBB) to the delay in antinociceptive effect of morphine in rats. Methods. Unbound morphine concentrations were monitored in venous blood and in brain extracellular fluid (ECF) using microdialysis (MD) and in arterial blood by regular sampling. Retrodialysis by drug was used for in vivo calibration of the MD probes. Morphine was infused (10 or 40 mg/kg) over 10 min intravenously. Nociception, measured by the electrical stimulation vocalisation method, and blood gas status were determined. Results. The half-life of unbound morphine in striatum was 44 min compared to 30 min in venous and arterial blood (p 〈 0.05). The BBB equilibration of morphine, expressed as the ratio of areas under the curve between striatum and venous blood, was less than unity (0.28 ± 0.09 and 0.22 ± 0.17 for 10 and 40 mg/kg), respectively, indicating active efflux of morphine across the BBB. The concentration-effect relationship exhibited a clear hysterisis with an effect delay half-life of 32 and 5 min based on arterial blood and brain ECF concentrations, respectively. Conclusions. Eighty five percent of the effect delay was caused by morphine transport across the BBB, indicating possible involvement of rate limiting mechanisms at the receptor level or distributional phenomena for the remaining effect delay of 5 min.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026414713509
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  • 16
    Electronic Resource
    Electronic Resource
    Confidence Interval Criteria for Assessment of Dose Proportionality (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1278-1283 
    Details
    ISSN: 1573-904X
    Keywords: bioequivalence ; dose proportionality ; mixed effects model ; pharmacokinetics ; power model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The aim of this work was a pragmatic, statistically sound and clinically relevant approach to dose-proportionality analyses that is compatible with common study designs. Methods. Statistical estimation is used to derive a (1-α)% confidence interval (CI) for the ratio of dose-normalized, geometric mean values (Rdnm) of a pharmacokinetic variable (PK). An acceptance interval for Rdnm defining the clinically relevant, dose-proportional region is established a priori. Proportionality is declared if the CI for Rdnm is completely contained within the critical region. The approach is illustrated with mixed-effects models based on a power function of the form PK = β0 • Doseβ1; however, the logic holds for other functional forms. Results. It was observed that the dose-proportional region delineated by a power model depends only on the dose ratio. Furthermore, a dose ratio (ρ1) can be calculated such that the CI lies entirely within the pre-specified critical region. A larger ratio (ρ2) may exist such that the CI lies completely outside that region. The approach supports inferences about the PK response that are not constrained to the exact dose levels studied. Conclusion. The proposed method enhances the information from a clinical dose-proportionality study and helps to standardize decision rules.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026451721686
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  • 17
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of a Hematoregulatory Peptide (SK&F 107647) in Healthy Male Volunteers and in Patients with Colorectal or Pancreatic Adenocarcinoma Not Amenable to Standard Therapy (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 385-390 
    Details
    ISSN: 1573-904X
    Keywords: SK&F 107647 ; peptide ; pharmacokinetics ; hematore gulatory ; adenocarcinoma ; cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To describe the pharmacokinetics of SK&F 107647, a synthetichematoregulatory peptide, in healthy volunteers and in patientswith adenocarcinoma.Methods. SK&F 107647 pharmacokinetics were evaluated in 2dose-escalation studies. Volunteers received SK&F 107647 as single15-minute iv infusion doses of 1, 10, 100, 500, and 1000 μg/kg. Cancerpatients received 2-hour iv infusions of 0.001, 0.01, 0.1 and 1μg/kg once daily for 10 days. Drug concentrations were quantified in plasmaand urine of healthy volunteers and on days 1 and 10 in plasma ofcancer patients receiving the two top dose levels.Results. In volunteers, mean clearance (CL) ranged from 76.7 to 101ml/hour/kg; mean volume of distribution at steady-state (Vss)rangedfrom 175 to 268 ml/kg. Most of the administered dose was renallyexcreted as intact peptide within 24 hours postinfusion. In patients,mean CL was 57.6 ml/hour/kg, mean Vss ranged from 128 to 150ml/kg and terminal half-life from 2.1 to 3.4 hours. There was littleaccumulation of drug. In both studies, linear pharmacokinetics wasobserved. Clearance approached normal glomerular filtration rate(GFR) in volunteers and correlated with creatinine clearance incancer patients.Conclusions. SK&F 107647 exhibits linear pharmacokinetics, a smallVss, and clearance, primarily renal, approaching normal GFR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007512617139
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  • 18
    Electronic Resource
    Electronic Resource
    A Human Physiologically-Based Model for Glycyrrhzic Acid, A Compound Subject to Presystemic Metabolism and Enterohepatic Cycling (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1516-1525 
    Details
    ISSN: 1573-904X
    Keywords: glycyrrhizic acid ; modeling ; enterohepatic cycling ; PBPK ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To analyze the role of the kinetics of glycyrrhizic acid (GD) in its toxicity. A physiologically-based pharmacokinetic (PBPK) model that has been developed for humans. Methods. The kinetics of GD, which is absorbed as glycyrrhetic acid (GA), were described by a human PBPK model, which is based on a rat model. After rat to human extrapolation, the model was validated on plasma concentration data after ingestion of GA and GD solutions or licorice confectionery, and an additional data derived from the literature. Observed interindividual variability in kinetics was quantified by deriving an optimal set of parameters for each individual. Results. The a-priori defined model successfully forecasted GA kinetics in humans, which is characterized by a second absorption peak in the terminal elimination phase. This peak is subscribed to enterohepatic cycling of GA metabolites. The optimized model explained most of the interindividual variance, observed in the clinical study, and adequately described data from the literature. Conclusions. Preclinical information on GD kinetics could be incorporated in the human PBPK model. Model simulations demonstrate that especially in subjects with prolonged gastrointestinal residence times, GA may accumulate after repeated licorice consumption, thus increasing the health risk of this specific subgroup of individuals.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007661209921
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  • 19
    Electronic Resource
    Electronic Resource
    Population Pharmacokinetic/ Pharmacodynamic Modeling of Cetrorelix, a Novel LH-RH Antagonist, and Testosterone in Rats and Dogs (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 328-335 
    Details
    ISSN: 1573-904X
    Keywords: luteinising hormone-releasing hormone (LH-RH) antagonist ; cetrorelix ; pharmacokinetics ; population PK/PD-modeling ; testosterone ; rat ; dog
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Population models for thepharmacokinetic-pharmacodynamic relationship for cetrorelix (CET), a luteinising hormone-releasinghormone (LH-RH) antagonist, and the pharmacodynamic response ontestosterone production were investigated in rats and dogs. Methods. The plasma concentrations of CET and testosterone weredetermined after intravenous and subcutaneous injections. Thepopulation PK/PD-models were developed using P-PHARM software. Results. Absolute bioavailability of cetrorelix was 100% in rats and97% in dogs. In rats, the pharmacokinetics was explained by atwo-compartment model with saturable absorption, while athree-compartment model was used in dogs. Testosterone suppression in both specieswas described by a sigmoid Emax model with maximum effect (Emax)considered as total hormonal suppression. The duration of testosteronesuppression in rats was longer at higher doses. The populationelimination half-lifes after iv-dose were 3.0 h in rats and 9.3 h in dogs.Population mean estimates of IC50 were 1.39 and 1.24 ng/ml in ratsand dogs, respectively. Conclusions. A population pharmacokinetic model was developed toexplain the dissolution rate limited absorption from the injection site.The suppression of testosterone could be described by an indirectinhibitory sigmoid Emax model. In both species 1-2 ng/ml CET inplasma was necessary to suppress testosterone production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007557207590
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  • 20
    Electronic Resource
    Electronic Resource
    Bioequivalence of Methylphenidate Immediate-Release Tablets Using a Replicated Study Design to Characterize Intrasubject Variability (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 381-384 
    Details
    ISSN: 1573-904X
    Keywords: methylphenidate ; average bioequivalence ; individual bioequivalence ; human ; pharmacokinetics ; replicated design
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To determine the relative bioavailability of two marketed,immediate-release methylphenidate tablets. The study used a replicatedstudy design to characterize intrasubject variability, and determinebioequivalence using both average and individual bioequivalencecriteria. Methods. A replicated crossover design was employed using 20subjects. Each subject received a single 20 mg dose of the reference tableton two occasions and two doses of the test tablet on two occasions.Blood samples were obtained for 10 hr after dosing, and plasma wasassayed for methylphenidate by GC/MS. Results. The test product was more rapidly dissolved in vitro and morerapidly absorbed in vivo than the reference product. The mean Cmaxand AUC(0 − ∞) differed by 11% and 9%, respectively. Using anaverage bioequivalence criterion, the 90% confidence limits for theLn-transformed Cmax and AUC(0 − ∞), comparing the two replicatesof the test to the reference product, fell within the acceptable range of80–125%. Using an individual bioequivalence criterion the test productfailed to demonstrate equivalence in Cmax to the reference product. Conclusions. The test and reference tablets were bioequivalent usingan average bioequivalence criterion. The intrasubject variability of thegeneric product was greater and the subject-by-formulation interactionvariance was borderline high. For these reasons, the test tablets werenot individually bioequivalent to the reference tablets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007560500301
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  • 21
    Electronic Resource
    Electronic Resource
    In Vivo Specific Binding Characteristics and Pharmacokinetics of a 1,4-Dihydropyridine Calcium Channel Antagonist in the Senescent Mouse Brain (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 844-850 
    Details
    ISSN: 1573-904X
    Keywords: 1,4-dihydropyridine calcium channel antagonist ; (+)-[3H]PN 200-110 ; senescence-accelerated prone mouse ; brain concentration ; pharmacokinetics ; in vivo receptor binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the in vivo specific binding andpharmacokinetics of a 1,4-dihydropyridine (DHP) calcium channel antagonist, PN200-110, in the senescent brain, using senescence-accelerated pronemice (SAMP8) and senescence-resistant mice (SAMR1). Methods. Blood, brain, and heart samples were taken periodically fromSAMR1 and SAMP8 following intravenous injection of (+)-[3H]PN200-110, and the concentration of (+)-[3H]PN 200-110 in the plasmaand tissues was determined. In addition, the in vivo specific bindingof (+)-[3H]PN 200-110 in the brains of SAMR1 and SAMP8 wasmeasured periodically after intravenous injection of the radioligand. Results. There was very little significant difference between SAMR1and SAMP8 in terms of the half-life (t1/2), total body clearance (CLtot),steady-state volume of distribution (Vdss), and AUC for the plasmaconcentration of (+)-[3H]PN 200-110 after intravenous injection ofthe radioligand. The brain concentration (AUCbrain) for (+)-[3H]PN200-110 and the brain/plasma AUC ratio (AUCbrain/AUCplasma) weresignificantly lower in SAMP8 than in SAMR1, and the heartconcentration (AUCheart) and the heart/plasma AUC ratio (AUCheart/AUCplasma)were similar in both strains. Also, the brain/plasma unbound AUCratio (AUCbrain/AUCplasma-free) for (+)-[3H]PN 200-110 wassignificantly lower in SAMP8 than in SAMR1. The in vivo specific binding(AUCspecific binding, maximal number of binding sites: Bmax) of(+)-[3H]PN 200-110 was significantly lower in brain particulate fractionsof SAMP8 than SAMR1. Conclusions. The concentration and in vivo specific binding of(+)-[3H]PN 200-110 was significantly reduced in the senescent brain. Thesimultaneous analysis of the concentrations of centrally acting drugsand the in vivo specific binding in the brain in relation to theirpharmacokinetics may be valuable in evaluating their CNS effects.
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    URL: http://dx.doi.org/10.1023/A:1007512426420
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  • 22
    Electronic Resource
    Electronic Resource
    Potential Role of P-Glycoprotein in Affecting Hepatic Metabolism of Drugs (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 903-905 
    Details
    ISSN: 1573-904X
    Keywords: P-glycoprotein ; hepatic metabolism ; pharmacokinetics ; first-pass metabolism ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007570517183
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  • 23
    Electronic Resource
    Electronic Resource
    An Isolated In-Situ Rat Head Perfusion Model for Pharmacokinetic Studies (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 127-134 
    Details
    ISSN: 1573-904X
    Keywords: in-situ head perfusion ; pharmacokinetics ; red blood cells ; water
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To develop a viable, single pass rat head perfusion modeluseful for pharmacokinetic studies. Methods. A viable rat head preparation, perfused with MOPS-bufferedRinger's solution, was developed. Radiolabelled markers (red bloodcells, water and sucrose) were injected in a bolus into the internalcarotid artery and collected from the posterior facial vein over 28minutes. The double inverse Gaussian function was used to estimatethe statistical moments of the markers. Results. The viability of the perfusion was up to one hour, with optimalperfusate being 2% bovine serum albumin at 37°C, pH 7.4. Thedistribution volumes for red blood cells, sucrose and water (from all studies,n = 18) were 1.0 ± 0.3ml, 6.4 ± 4.2ml and 18.3 ± 11.9ml, respectively.A high normalised variance for red blood cells (3.1 ± 2.0) suggestsa marked vascular heterogeneity. A higher normalised variance forwater (6.4 ± 3.3) is consistent with additional diffusive/permeabilitylimitations. Conclusions. Analysis of the physiological parameters derived fromthe moments suggested that the kinetics of the markers were consistentwith distribution throughout the head (weight 25g) rather than justthe brain (weight 2g). This model should assist in studying solutepharmacokinetics in the head.
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    URL: http://dx.doi.org/10.1023/A:1007500910566
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  • 24
    Electronic Resource
    Electronic Resource
    Physiological Modeling of Altered Pharmacokinetics of a Novel Anticancer Drug, UCN-01 (7-Hydroxystaurosporine), Caused by Slow Dissociation of UCN-01 from Human α1-Acid Glycoprotein (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 553-564 
    Details
    ISSN: 1573-904X
    Keywords: α1-acid glycoprotein ; protein binding ; dissociation rate ; species difference ; physiological model ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The extremely low clearance and small distribution volumeof UCN-01 in humans could be partly due to the high degree of bindingto hAGP (1,2). The quantitative effects of hAGP on the pharmacokineticsof UCN-01 at several levels of hAGP and UCN-01 were estimatedin rats given an infusion of hAGP to mimic the clinical situation anda physiological model for analysis was developed. Methods. The plasma concentrations of UCN-01 (72.5–7250 nmol/kgiv) in rats given an infusion of hAGP, 15 or 150 nmol/h/kg, weremeasured by HPLC. Pharmacokinetic analysis under conditionsassuming rapid equilibrium of protein binding and incorporating thedissociation rate was conducted. Results. The Vdss and CLtot of UCN-01 (725 nmol/kg iv) in ratsgiven an infusion of hAGP, 150 nmol/h/kg, fell to about 1/250 and 1/700that in control rats. The Vdss and CLtot following 72.5–7250nmol/kg UCN-01 to rats given 150 nmol/h/kg hAGP were 63.9–688ml/kg and 3.18–32.9 ml/h/kg, respectively, indicating non-linearitydue to saturation of UCN-01 binding. The CLtot estimated by thephysiological model assuming rapid equilibrium of UCN-01 bindingto hAGP, was six times higher than the observed value while the CLtotestimated by the model incorporating koff, measured using DCC, wascomparable with the observed value. Conclusions. These results suggest that the slow dissociation ofUCN-01 from hAGP limits its disposition and elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007512832006
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  • 25
    Electronic Resource
    Electronic Resource
    Influence of Stereoselective Pharmacokinetics in the Development and Predictability of an IVIVC for the Enantiomers of Metoprolol Tartrate (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1019-1025 
    Details
    ISSN: 1573-904X
    Keywords: IVIVC ; racemate ; enantiomers ; metoprolol ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To investigate the ability of an IVIVC developedwith a racemate drug as well as each enantiomer in predicting the invivo enantiomer drug performance. Methods. Dissolution of metoprolol extended releasetablets with different release characteristics (e.g., fast (F),moderate (M), and slow (S)) was performed using USP ApparatusI, pH 1.2, 50 rpm. Metoprolol racemate tablets (S, M, and F, 100 mg) and 50mg oral solution were administered to healthy volunteers, blood samples werecollected over 24 (solution) and 48 (tablet) hours and assayed. IVIVC modelsdeveloped were: (1) Racemate-fraction of drug dissolved (FRD) vsRacemate-fraction of drug absorbed (FRA), (2) R-FRD vs R-FRA, and (3) S-FRDvs S-FRA for combinations of formulations (S/M/F, S/M, S/F, and M/F).Enantiomer Cmax and AUC prediction errors (PEs) were estimated for modelevaluation after convolution of in vivo release rates. Results. The R-IVIVC and S-IVIVC accurately predicted theR- and S-metoprolol pharmacokinetic profiles, respectively. The averagedprediciton errors (PE) for the enantiomer Cmax and AUC were less than10% for S/M/F, M/F, and S/F IVIVC models. Racemate-IVIVC (M/F) wasable to predict S-enantiomer with an average %PE of 2.52 for S-Cmaxand 4.3 for S-AUC. However, the racemate-IVIVC was unable to predict theR-enantiomer pharmacokinetic profile. Conclusions. Metoprolol racemate data cannot be used toaccurately predict R-enantiomer drug concentrations. However, the racematedata was predictive of the active stereoisomer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007595725360
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  • 26
    Electronic Resource
    Electronic Resource
    2-Methylisoborneol disposition in three strains of catfish: absence of biotransformation (2000)
    Springer
    Fish physiology and biochemistry 23 (2000), S. 225-232 
    Details
    ISSN: 1573-5168
    Keywords: methylisoborneol ; catfish ; cytochrome P450 ; biotransformation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 2-Methylisoborneol (MIB) and structurally related terpenoid compounds are responsible for millions of dollars of lost revenue to catfish farmers. In an attempt to determine enzymatic pathways of biotransformation and elimination of MIB, the in vitro metabolism of MIB was examined in the Ulvade strain of channel catfish (Ictalurus punctatus). Although cytochrome P450 (CYP) activities were observed and correlated with expression of specific isoforms (i.e. steroid hydroxylation and CYP3A expression), no metabolites of MIB were observed. To determine whether extrahepatic biotransformation may be occurring the in vivo metabolism and disposition of 14C-MIB was examined in Uvalde, USDA-103 channel catfish, and a channel catfish X blue catfish (Ictalurus furcatus) hybrid species. Confirming in vitro hepatic studies, no metabolites were observed in plasma from animals treated with an intra-arterial dose of 14C-MIB. 14C-MIB elimination was predicted using a two compartment model in each strain of fish. There was no significant difference in terminal half-lives between strains but possible differences in total body clearance and apparent volumes of distribution which may be related to higher lipid content in the hybrids. Results of these studies indicate biotransformation has no involvement in MIB elimination and that other physiological processes may play a more significant role in MIB disposition within Ictalurid fish species.
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    URL: http://dx.doi.org/10.1023/A:1007834720306
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  • 27
    Electronic Resource
    Electronic Resource
    Relationship between in vivo drug exposure of the tumor interstitium and inhibition of tumor cell growth in vitro: a study in breast cancer patients (2000)
    Springer
    Breast cancer research and treatment 60 (2000), S. 211-217 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; 5-fluorouracil ; methotrexate ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A novel approach is described to simulate effect site pharmacodynamics of anticancer drugs. This approach is based on (i) the in vivo measurement of unbound, interstitial drug pharmacokinetics (PK) in solid tumor lesions in patients and (ii) a subsequent pharmacodynamic (PD) simulation of the time versus drug concentration profile in an in vitro setting. For this purpose, breast cancer cells (MCF-7) were exposed in vitro to the time versus interstitial tumor concentration profiles of 5-fluorouracil (5-FU) and methotrexate (MTX) from primary breast cancer lesions in patients. This led to a maximal reduction in the viable cell count of 69 on day 4, and of 71 on day 7 for 5-FU and MTX, respectively. This effect was dependent on the initial cell count and was characterized by a high interindividual variability. For 5-FU there was a significant correlation between the maximum antitumor effect and the intratumoral AUC (r = 0.82, p = 0.0005), whereas no correlation could be shown for MTX (r = 0.05, p = 0.88). We conclude, that the in-vivo-PK / in-vitro-PD model presented in this study may provide a rational approach for describing and predicting pharmacodynamics of cytotoxic drugs at the target site. Data derived from this approach support the concept that tumor penetration of 5-FU may be a response-limiting event, while the response to MTX may be determined by events beyond interstitial fluid kinetics.
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    URL: http://dx.doi.org/10.1023/A:1006497202341
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  • 28
    Electronic Resource
    Electronic Resource
    Drug Interactions with Colesevelam Hydrochloride, a Novel, Potent Lipid-Lowering Agent (2000)
    Springer
    Cardiovascular drugs and therapy 14 (2000), S. 681-690 
    Details
    ISSN: 1573-7241
    Keywords: colesevelam hydrochloride ; bile acid sequestrant ; drug interactions ; pharmacokinetics ; digoxin ; warfarin ; quinidine ; verapamil ; metoprolol ; valproic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Colesevelam hydrochloride (colesevelam) is a novel, potent, bile acid–binding agent that has been shown to lower LDL cholesterol a mean of 19% at a dose of 3.8 g/d. We studied the pharmacokinetics of colesevelam coadministered with six drugs: digoxin and warfarin, agents with narrow therapeutic indices; sustained-release verapamil and metoprolol; quinidine, an antiarrhythmic with a narrow therapeutic index; and valproic acid, an antiseizure medication. Six individual studies were single-dose, crossover, with or without a 4.5-g dose of colesevelam. Plasma levels were determined using validated analytical methods. Values for the ratio of ln[AUC(0-t)] with and without colesevelam were 107% for quinidine, 102% for valproic acid, 89% for digoxin, 102% for warfarin, 82% for verapamil, and 112% for metoprolol. Values for the ratio of ln[Cmax] with and without colesevelam were 107% for quinidine, 92% for valproic acid, 96% for digoxin, 99% for warfarin, 69% for verapamil, and 112% for metoprolol. The 90% confidence intervals for these ratios and for values of ln[AUC(0-inf)] that could be determined were within the 80–125% range, with the exception of verapamil. In this study, verapamil had great interindividual variability, with a 28-fold range in Cmax and an 11-fold range in AUC(0-t). In summary, pharmacokinetic studies with colesevelam did not show clinically significant effects on absorption of six other coadministered drugs.
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    URL: http://dx.doi.org/10.1023/A:1007831418308
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  • 29
    Electronic Resource
    Electronic Resource
    Sequential Group Trial to Determine Gastrointestinal Site of Absorption and Systemic Exposure of Azathioprine (2000)
    Springer
    Digestive diseases and sciences 45 (2000), S. 1601-1607 
    Details
    ISSN: 1573-2568
    Keywords: azathioprine ; 6-mercaptopurine ; gastrointestinal ; pharmacokinetics ; bioavailability ; inflammatory bowel disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Azathioprine (AZA) is used in the treatment of patients with refractory inflammatory bowel disease; however, its use is limited because of systemic toxicity associated with long-term use. Ileocecal delivery of AZA might be advantageous if local intestinal therapeutic effects could be provided with decreased systemic side effects. Decreased cecal systemic absorption would allow higher dosages of AZA to be administered. A two-phase study was performed to compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following administration of AZA into the stomach, jejunum, and cecum and to compare the systemic exposure to AZA and 6-MP following administration of three different dosages of AZA into the cecum. In phase I, six healthy male volunteers received three 50 mg sequential doses of AZA via an oral tube directly placed into the stomach, jejunum, and cecum, respectively. In phase II, six healthy male volunteers received three different dosages (50, 300, 600 mg of AZA) into the cecum. Plasma concentrations of AZA and 6-MP at various times were quantified and area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were determined. No significant differences in the AUC of AZA were seen at the different sites. The AUC of 6-MP following administration of AZA into the jejunum (67.0 ± 30.1 ng×hr/ml) was higher compared to the stomach (39.9 ± 38.1 ng/hr/ml) and cecum (29.2 ± 10.9 ng×hr/ml). Jejunal absorption was 68% higher than absorption from the stomach and 129% higher than that of the cecum. Gastric absorption was 27% higher than that of the cecum. Increased dosages given into the cecum resulted in increased AUCs of AZA and 6-MP. The AUCs of AZA following 50, 300, and 600 mg dosages were 16.9 ± 7.4, 52.3 ± 67.2, and 132 ± 151 ng×hr/ml, respectively, and the AUCs of 6-MP were 22.2 ± 14.9, 63.4 ± 50.6, and 104 ± 115 ng×hr/ml, respectively. Systemic exposure to 6-MP is reduced following administration of AZA into the cecum, most likely secondary to reduced absorption of 6-MP from the colon. Higher dosages of AZA presented to the cecum do result in increased systemic absorption, but may still allow more drug to be administered with less toxicity than the same dose received orally.
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    URL: http://dx.doi.org/10.1023/A:1005573229786
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  • 30
    Electronic Resource
    Electronic Resource
    Absorption and Disposition of a Selective Aldosterone Receptor Antagonist, Eplerenone, in the Dog (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1426-1431 
    Details
    ISSN: 1573-904X
    Keywords: eplerenone ; selective aldosterone receptor antagonist ; dog ; pharmacokinetics ; absorption
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The present study was conducted to characterize the pharmacokinetics of eplerenone (EP), a selective aldosterone receptor antagonist, and its open lactone ring form in the dog. Methods. Pharmacokinetic studies of EP were conducted in dogs following i.v., oral, and rectal dosing (15 mg/kg) and following intragastric, intraduodenal, intrajejunal, and intracolonic dosing (7.5 mg/kg). Results. After oral administration, the systemic availability of EP was 79.2%. Systemic availabilities following administration via other routes were similar to that following oral administration. The half-life and plasma clearance of EP were 2.21 hr and 0.329 l/kg/hr, respectively. Plasma concentrations of the open lactone ring form were lower than EP concentrations regardless of the route of administration. The C-14 AUC in red blood cells was approximately 64% and 68% of the plasma AUC for i.v. and oral doses. Percentages of the dose excreted as total radioactivity in urine and feces were 54.2% and 40.6%, respectively, after i.v. administration, and 40.7% and 52.3%, respectively, after oral administration. The percentages of the dose excreted in urine and feces as EP were 13.7% and 2.5%, respectively, after i.v. administration, and 2.1% and 4.6% after oral administration, respectively. Approximately 11% and 15% of the doses were excreted as the open form following i.v. and oral doses. Conclusions. EP was rapidly and efficiently absorbed throughout the gastrointestinal tract, resulting in a good systemic availability. The drug did not preferentially accumulate in red blood cells. EP was extensively metabolized; however, first-pass metabolism after oral and rectal administration was minimal. EP and its metabolites appear to be highly excreted in the bile.
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    URL: http://dx.doi.org/10.1023/A:1007597713530
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  • 31
    Electronic Resource
    Electronic Resource
    Safety, Toxicokinetics and Tissue Distribution of Long-Term Intravenous Liposomal Amphotericin B (ambisome®): A 91-day Study in Rats (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1494-1502 
    Details
    ISSN: 1573-904X
    Keywords: amphotericin B ; liposomes ; pharmacokinetics ; toxicokinetics ; tissue distribution ; toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Amphotericin B in small, unilamellar liposomes (AmBisome) is safer and produces higher plasma concentrations than other formulations. Because liposomes may increase and prolong tissue exposures, the potential for drug accumulation or delayed toxicity after chronic AmBisome was investigated. Methods. Rats (174/sex) received intravenous AmBisome (1, 4, or 12 mg/kg), dextrose, or empty liposomes for 91 days with a 30-day recovery. Safety (including clinical and microscopic pathology) and toxicokinetics in plasma and tissues were evaluated. Results. Chemical and histopathologic changes demonstrated that the kidneys and liver were the target organs for chronic AmBisome toxicity. Nephrotoxicity was moderate (urean nitrogen [BUN] ≤51 mg/dl; creatinine unchanged). Liposome-related changes (vacuolated macrophages and hypercholesterolemia) were also observed. Although plasma and tissue accumulation was nonlinear and progressive (clearance and volume decreased, half-life increased with dose and time), most toxic changes occurred early, stabilized by the end of dosing, and reversed during recovery. There were no delayed toxicities. Concentrations in liver and spleen greatly exceeded those in plasma; kidney and lung concentrations were similar to those in plasma. Elimination half-lives were 1-4 weeks in all tissues. Conclusions. Despite nonlinear accumulation, AmBisome revealed predictable hepatic and renal toxicities after 91 days, with no new or delayed effects after prolonged treatment at high doses that resulted in plasma levels 〉200 μg/ml and tissue levels 〉3000 μg/g.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007605024942
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    Electronic Resource
    Biodistribution of Amphotericin B When Delivered Through Cholesterol Hemisuccinate Vesicles in Normal and A. Fumigatus Infected Mice (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 1236-1242 
    Details
    ISSN: 1573-904X
    Keywords: aspergillosis ; pharmacokinetics ; amphotericin B ; biodistribution ; liposomes ; cholesterol hemisuccinate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. This study compared the biodistribution of two amphotericin B formulations in normal and Aspergillus infected mice. Amphotericin B cholesterol hemisuccinate vesicles (ABCV) which reduces the toxicity of amphotericin B and thereby enhances its therapeutic efficacy in a murine model of aspergillosis was compared with conventional amphotericin B deoxycholate suspension (AmBDOC). Methods. ABCV (12 mg/kg wt) and AmBDOC (2 mg/kg wt) were intravenously administered to normal and A.fumigatus infected mice. The concentration of amphotericin B in plasma and other organs was determined at different time points. Results. It was observed that ABCV had a significantly different pharmacokinetic profile compared to conventional amphotericin B. In comparison to AmBDOC significantly lower levels of amphotericin B were observed in kidneys and plasma, the major target organs of toxicity. Animals receiving ABCV demonstrated high levels of amphotericin B in liver (38% retention till 48 h) and spleen (2.6% retention till 48 h) in comparison to AmBDOC (7.3% and 0.21% retention in liver and spleen respectively till 48 h). Biodistribution studies of ABCV in infected mice demonstrated that there was a moderate enhancement in levels of amphotericin B in liver, spleen, lungs and kidneys as compared to normal mice and the plasma levels were reduced. However, such observations were not made after AmBDOC administration to infected mice except for kidneys in which there was a marked increase in uptake as compared to normal mice. Conclusions. Our results suggest that prolonged retention of high concentrations of ABCV in reticuloendothelial system organs is the reason for its reduced toxicity. Enhanced localization of the drug at the infected site may lead to improvement in therapeutic efficacy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026418814417
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  • 33
    Electronic Resource
    Electronic Resource
    Evaluation of Using Dog as an Animal Model to Study the Fraction of Oral Dose Absorbed of 43 Drugs in Humans (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 135-140 
    Details
    ISSN: 1573-904X
    Keywords: oral absorption ; humans ; dogs ; rats ; interspecies scale-up ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To conduct a retrospective evaluation of using dog as ananimal model to study the fraction of oral dose absorbed (F) of 43drugs in humans and to briefly discuss potential factors that mighthave contributed to the observed differences in absorption. Methods. Mean human and dog absorption data obtained under fastedstate of 43 drugs with markedly different physicochemical andpharmacological properties and with mean F values ranging from 0.015 to1.0 were obtained from the literature. Correlation of F values betweenhumans and dogs was studied. Based on the same references, additionalF data for humans and rats were also obtained for 18 drugs. Results. Among the 43 drugs studied, 22 drugs were virtuallycompletely absorbed in both dogs and humans. However, the overallcorrelation was relatively poor (r2 = 0.5123) as compared to the earlier ratvs. human study on 64 drugs (r2 = 0.975). Several drugs showed muchbetter absorption in dogs than in humans. Marked differences in thenonliner absorption profiles between the two species were found forsome drugs. Also, some drugs had much longer Tmax values andprolonged absorption in humans than in dogs that might be theoreticallypredicted. Data on 18 drugs further support great similarity in F betweenhumans and rats reported earlier from our laboratory. Conclusions. Although dog has been commonly employed as ananimal model for studying oral absorption in drug discovery anddevelopment, the present study suggests that one may need to exercise cautionin the interpretation of data obtained. Exact reasons for the observedinterspecies differences in oral absorption remain to be explored.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007552927404
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  • 34
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    Electronic Resource
    Mechanism-Based Modeling of Functional Adaptation Upon Chronic Treatment with Midazolam (2000)
    Springer
    Pharmaceutical research 17 (2000), S. 321-327 
    Details
    ISSN: 1573-904X
    Keywords: benzodiazepines ; pharmacokinetics ; EEG ; operational model of agonism ; receptor binding ; muscimol-induced Cl−uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. A mechanism-based model is applied to analyse adaptivechanges in the pharmacodynamics of benzodiazepines upon chronictreatment in rats. Methods. The pharmacodynamics of midazolam was studied in ratswhich received a constant rate infusion of the drug for 14 days, resultingin a steady-state concentration of 102 ± 8 ng·ml−1. Vehicle treated ratswere used as controls. Concentration-EEG effect data were analysed onbasis of the operational model of agonism. The results were comparedto data obtained in vitro in a brain synaptoneurosomal preparation. Results. The relationship between midazolam concentration and EEGeffect was non-linear. In midazolam pre-treated rats the maximum EEGeffect was reduced by 51 ± 23 μV from the original value of 109 ±15 μV in vehicle treated group. Analysis of this change on basis ofthe operational model of agonism showed that it can be explained bya change in the parameter tissue maximum (Em) rather than efficacy(τ). In the in vitro studies no changes in density, affinity or functionalityof the benzodiazepine receptor were observed. Conclusions. It is concluded that the observed changes in theconcentration-EEG effect relationship of midazolam upon chronic treatmentare unrelated to changes in benzodiazepine receptor function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007505223519
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  • 35
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    Electronic Resource
    Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration (2000)
    Springer
    Bulletin of experimental biology and medicine 129 (2000), S. 359-361 
    Details
    ISSN: 1573-8221
    Keywords: acylprolyldipeptide ; GVS-111 ; pharmacokinetics ; blood-brain barrier permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Pharmacokinetics of GVS-111, a new acylprolyldipeptide with nootropic properties and its penetration across the blood-brain barrier were studied in rats using HPLC. It was found that the dipeptide is absorbed in the gastrointestinal tract, enters the circulation, and penetrates through the blood-brain barrier in an umodified state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02439270
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  • 36
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    Electronic Resource
    Synthese des D-Idomethylose-3-methyläthers. Desoxyzucker, 30. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 6-17 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Ausgehend vom α- und β-Mehtyl-D-galactosid-〈1,5〉 wurden jeweils auf zwei Wegen der α- und der β-Methyl-D-idomethylosid-〈1,5〉-3-methyläther bereitet. Das β-Derivat kristallisierte. Saure Hydrolyse der beiden Stoffe gab freien D-Idomethylose-3-methyläther als Sirup. Es liess sich ein krist. Osazon daraus gewinnen, womit alle vier theoretisch möglichen Osazone der Hexamethylose-3-methyläther der D-Reihe bekannt sind.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370103
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  • 37
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    Electronic Resource
    Teilsynthese von 11-Epi-corticosteron. Bestandteile der Nebennierenrinde und verwandte Stoffe, 86. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 45-58 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die Teilsynthese von 11-Epi-corticosteron und seinen Acetaten nach der Diazoketon-Methode, ausgehend vom 3β, 11α-Diacetoxyätiansäure-methylester wird beschrieben.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370107
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  • 38
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    Electronic Resource
    Über die tuberkulostatischen Eigenschaften der Hydrazide der Isonicotinsäure und der Benzoesäure. Metallionen und biologische Wirkung, 17. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 95-97 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Benzhydrazid schwächt die Wirkung von INH auf Tbc H37Rv deutlich ab. Zusatz von Cu‥ zu diesem System hebt diese Abschwächung wieder auf; darüber hinaus wird das nach dem 10. Tag mit INH allein zu beobachtende Wachstum stark zurückgedrängt. Ein ähnlicher Effekt ist auch durch Zusatz von Co‥ zu INH zu erreichen.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370111
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  • 39
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    Electronic Resource
    Über die Verwendung von Cellulose als Adsorbens für Blutplasma-Proteine aus wässeriger Lösung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 97-103 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The use of cellulose as an adsorbent for the proteins of plasma in aqueous solution has been investigated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370112
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  • 40
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    Electronic Resource
    Notiz über die Herstellung einiger Bis-formazane und Bis-tetrazoliumsalze (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 1-6 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Es wird die Herstellung von [3,3′-Dimethyl-diphenylen-(4,4′)]-bis-[N-(N′-phenyl)-formazyl-benzol],[3,3′-Dimethoxy-diphenylen-(4,4′)]-bis-[N-(N′-phenyl)-formazyl-benzol],[Diphenylen-(4,4′)]-bis-[N-(N′-phenyl)-formazyl-benzol], [Diphenyl-thioureyl-(4,4′)]-bis-[N(N′-phenyl)-formazyl-benzol], [Diphenyl-sulfoxydyl-(4,4′)]-bis-[N-(N′phenyl)-formazyl-benzol] und der entsprechenden Bis-tetrazoliumsalze beschrieben.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370102
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  • 41
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    Zur Kenntnis der Zucker-osazone. 4. Mitteilung. Anhydro-Derivate der Tagatose- bzw. Sorbose-phenylosazone und -phenylosotriazole (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 35-41 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die Abspaltung von 1 Mol Wasser aus Phenyl-osazonen und Phenyl-osotriazolen der Sorbose- und der Tagatose-Reihe führt zu-3, 6-Anhydro-Derivaten, deren Konstitution aufgeklärt werden konnte.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370105
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  • 42
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    Electronic Resource
    Zur Konstitution von Sarmutosid und Musarosid. Glykoside von Strophantus sarmentosus A. P. DC. 6. Mitteilung. Glykoside und Aglykone 121. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 76-89 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Sarmutosid (I) und Musarosid (II) enthalten dasselbe Aglykon und unterscheiden sich nur im Zuckeranteil. Das Aglykon wird als Sarmutogenin (V) bezeichnet. Im Sarmutosid ist es β-glykosidisch mit D-Sarmentose (IV) verknüpft, im Musarosid analog mit D-Digitalose (VII).
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370109
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  • 43
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    Electronic Resource
    Die Glykoside der Samen von Strophanthus caudatus (Burm. ex L.) Kurz. Glykoside und Aglykone, 122. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 103-112 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die Samen von Strophanthus caudatus (Burm. ex L.) Kurz gaben nach Einwirkung des wasserlöslichen Teils der darin enthaltenen Fermente ein Glykosidgemisch. Aus den äther- und chloroform löslichen Anteilen dieses Gemisches liess sich durch Adsorptionschromatographie als Hauptglykosid krist. Caudosid (0,246%) isolieren. Die Mutterlaugen gaben nach Trennung durch Verteilungschromatographie noch etwas krist. Divaricosid (0,031%). Neben diesen zwei Stoffen wurden noch kleine Mengen „Nebenprodukt H“ isoliert, das kein digitaloides Lacton darstellt, sowie Spuren „Kristallisat G“ und „Kristallisat J“. Die zwei letztgenannten Stoffe stellen wahrscheinlich digitaloide Lactone dar, doch ist ihre Reinheit unsicher.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370113
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  • 44
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    Electronic Resource
    Die Glykoside von Strophanthus mirabilis Gilg. 2.Mitteilung. Glykoside und Aglykone, 123. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 141-147 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Aus den Samen von Strophanthus mirabilis Gilg. wurden nach fermentativem Abbau Periplocymarin, Cymarin, Cymarol, Emi-cymarin und in sehr geringer Menge ein nicht identifizierter krist. Stoff vom Smp. 171-174° (Subst. A) isoliert. Im Chloroform-Alkohol-(2:1)-Extrakt wurden durch Papierchromatographie mindestens vier weitere Stoffe nachgewiesen.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370117
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  • 45
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    Electronic Resource
    Über Alkylenimin-Derivate. 6. Mitteilung. Über die partielle Reduktion von cyclischen Imiden (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 185-190 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: It is shown that LiAIH4 reduces cyclic imides, namely 3,3-disubstituted 2,5-dioxo-pyrrolidines and 2,6-dioxo-piperidines, primarily at the oxo-group not adjacent to the two substituents. Hydroxylactames are formed as the first reduction products. Similarly, the same oxygen atom is replaced by sulfur by reaction with P2S5. This behaviour is ascribed to steric hindrance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370122
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  • 46
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    Electronic Resource
    Sur l'aminolyse des amides. II. Action catalytique des acides (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 216-221 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: As an example of aminolysis of amides, the reaction between acetanilide and o-anisidine has been studied with special reference to the catalytic action of acids. In the case of a weak acid, the rate of aminolysis increases continuously as the concentration of the catalyzing acid is increased; on the other hand, in the case of a strong acid, the rate passes through a maximum value. A mechanism for aminolysis of amides, consistent with these facts, is suggested.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370126
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  • 47
    Electronic Resource
    Electronic Resource
    Synthesen in der Vitamin-K-Reihe I. Über totalsynthetisches Vitamin K1 (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 225-233 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Durch Kondensation von 2-Methyl-1,4-naphtohydrochinon mit synthetischem Isophytol wurde mittels Bortrifluoridätherat als Kondensationsmittel ein Vitamin K1 mit racemischer Seitenkette gewonnen. Dieses totalsynthetische racemische Vitamin K1 unterscheidet sich nur geringfügig vom Vitamin K1 mit optisch einheitlicher Phytylseitenkette. Die Verbindungen zeigen gleiche UV.- und IR.-Absorptionsspektren, und sie unterscheiden sich nicht im oxydativen Abbau. Sie besitzen am Vitamin-K-Mangelkücken und am Kaninchen mit Dicumarol-Hypoprothrombinämie die gleiche biologische Wirksamkeit.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370128
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  • 48
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    Untersuchungen über Komplexbildungsreaktionen in Lösung. Metallionen und biologische Wirkung, 20. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 239-241 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Es wurden die in einem Dialysierschlauch erfolgenden Reaktionen 1. Verschiedener Komplexbildner mit Cu‥, 2. des Alanins mit verschiedenen Metallionen vergleichend durch Ermittlung der nach aussen diffundierenden Ionen untersucht.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370130
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  • 49
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    Beiträge zum Problem der Ähnlichkeit bei Komplexverbindungen. Metallionen und biologische Wirkung, 19. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 234-239 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Es wird das Problem der Ähnlichkeit bei Komplexverbindungen erörtert und die aus Ni(CN)2 und β-(2-Thienyl)-äthylamin zu gewinnende Verbindung beschrieben.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370129
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  • 50
    Electronic Resource
    Electronic Resource
    Collecteur de fractions automatique pour chromatographie (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 242-245 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A pressure-operated chromatographic device, fitted with a float valve which shuts off the pressure system when the reservoir of the eluant is empty, and a constant-volume automatic fraction collector are described.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370131
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  • 51
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    Action de la phosphoglucomutase du muscle sur des acides aldose-1-phosphoriques. Transformation de l'acide galactose-1-phosphorique (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 246-250 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: La phosphoglucomutase du muscle de lapin convertit l'acide α-galactose-1-phosphorique en une substance acidostable qui est vraisemblablement l'acide galactose-6-phosphorique.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370132
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  • 52
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    Über Steroide und Sexualhormone. 198. Mitteilung. Herstellung und Konfiguration der Oxyde des Δ5-3α-Oxy-cholestens (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 258-266 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Im Zusammenhang mit Untersuchungen über den sterischen Verlauf von Reaktionen an Steroid-epoxyden wurden die beiden Oxyde des Δ5-3 α-Oxy-cholestens („epi“-Cholesterin) hergestellt und ihre Konfiguration aufgeklärt.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370134
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  • 53
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    Über Steroide und Sexualhormone. 197. Mitteilung. Über die Dehydrierung von α-Dihydro-ergosterin-acetat mit Quecksilber (II)-acetat und Selendioxyd (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 250-257 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Bei der Oxydation von Δ7;22 β-Acetoxy-ergostadien (α-Dihydroergosterin-acetat (II)) mit Selendioxyd in Äther-Eisessig entsteht neben dem 8,14-ungesättigten-7 α-Oxy-Derivat Vb ein weiterer, isomerer Allylalkohol. Es konnten Anhaltspunkte dafür gewonnen werden, dass dieser Verbindung die Konstitution eines 7,8-ungesättigten 9-Oxy-ergostan-Derivates IV zukommt. Die beiden Oxydationsprodukte stellen Zwischenstufen bei der Dehydrierung von α-Dihydroergosterin-acetat (II) mit Selendioxyd zu Ergosterin B3 (III) und Ergosterin-D-acetat (I) dar.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370133
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    Zur Kenntnis der Sesquiterpene und Azulene. 107. Mitteilung. Synthese einiger Abbauprodukte des Cedrens (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 266-271 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Zwei aliphatische Abbauprodukte des tricyclischen Sesquiterpens, Cedren, die α,α-Dimethyl-β-carboxy-adipinsäure (III) sowie die 2,2-Dimethyl-3-carboxy-6-keto-heptansäure (II) wurden synthetisiert; die racemische Verbindung II wurde in ihre optischen Antipoden gespalten.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370135
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  • 55
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    Zur Kenntnis der Sesquiterpene und Azulene. 108. Mitteilung. Zur Konstitution einiger Azulen-carbonsäuren (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 271-281 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die Konstitution einiger Azulen-carbonsäuren wurde durch ihre Überführung in die entsprechenden Isopropyl-azulene bestätigt.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370136
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  • 56
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    Contribution à l'étude du système quinaire Ca++—NH4+—H+—NO3-—PO4---—H2O. X. Les solutions simultanément saturées à 25° de phosphate monocalcique et d'un nitrate (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 282-299 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Dans le système quinaire Ca++—NH4+—H+—NO3-—PO4---—H2O, on peut obtenir des solutions qui sont simultanément saturées de phosphate monocalcique et d'un nitrate simple et double des ions Ca++ et NH4+. Nous avons déterminé la composition de solutions saturées à 25° de deux phases solides, soit de: .
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370137
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  • 57
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    Contribution à l'étude du système quinaire Ca++—NH4+—H+—NO3-—PO4---—H2O. XI. Méthode d'interpolation pour établir, dans le diagramme à 4 dimensions, les coordonnées de solutions saturées de deux phases solides (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 299-306 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Nous décrivons un procédé d'interpolation permettant d'établir, dans le système quinaire Ca++—NH4+—H+—NO3-—PO4---—H2O, la composition de solutions simultanément saturées de phosphate monocalcique et d'un nitrate simple ou double des ions Ca++ et NH+. Cette méthode utilise le diagramme de solubilité du système quaternaire Ca++—NH4+—H+—NO3-—H2O et des diagrammes indiquant la solubilité du phosphate monocalcique dans des solutions aqueuses de Ca(NO3)2 + NH4NO3 + HNO3.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370138
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  • 58
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    Rauhimbin und Isorauhimbin, zwei neue Alkaloide aus Rauwolfia serpentina Benth. 2. Mitteilung über Rauwolfia-Alkaloide (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 314-320 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Es wird die Isolierung von zwei neuen Alkaloiden aus Rauwolfia serpentina Benth. beschrieben. Die Bruttoformel C21H26O3N2 sowie physikalische und chemische Eigenschaften kennzeichnen sie als Isomere des Yohimbins, was durch die Bezeichnung Rauhimbin und Isorauhimbin zum Ausdruck gebracht wird.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370140
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  • 59
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    16α-Oxy-cortexon. Mikrobiologische Reaktionen, 3. Mitt (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 321-326 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Submerged cultures of several species of streptomyces under aerobic conditions converted cortexone into 16α-hydroxy-cortexone. The diacetate of this new compound is identical with a compound obtained by Hirschmann et al. in a chemical multistage synthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370141
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  • 60
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    Untersuchungen über Organextrakte. 24. Mitteilung. Über das hormonal aktive Prinzip eines feminisierenden Hodentumors (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 327-332 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Aus einem gutartigen Hodentumor, der histologisch betrachtet an Nebennierenrindengewebe erinnerte und welcher beim Patienten deutliche Zeichen der Feminisierung (Gynaekomastie) erzeugte, wurde Östradiol als Dibenzoat isoliert. Die Konzentration an Östradiol in diesem Tumor ist mindestens 130 000mal grösser als der Gehalt normaler menschlicher Testes an demselben weiblichen Sexualhormon. Die in der Literatur vertretenen Ansichten über die hormonale Wirkungsweise solcher Tumoren werden unter Berücksichtigung dieser neuen experimentellen Befunde diskutiert.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370142
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  • 61
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    Über eine biologische Bedeutung der Gallenfarbstoffe. Bilirubin und Biliverdin als Antioxydantien für das Vitamin A und die essentiellen Fettsäuren (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 306-313 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Rats with a thoracic duct fistula absorb vitamin A and β-carotene very poorly in the total absence of bile from the intestine. Administration of taurocholic acid improves the degree of absorption but fails to raise it to its normal level. It was demonstrated in vitro that small quantities of bilirubin and biliverdin exert a stabilizing action towards vitamin A. Consequently, it may be assumed that the bile pigments play the same role in vivo, serving as natural antioxidants which protect easily oxidizable substances from destruction in the intestinal tract.
    Additional Material: 12 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370139
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  • 62
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    Contribution à l'étude du potentiel de l'or (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 333-344 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Nous avons tout d' cherché à déterminer le potentiel normal de l'ion aurique en solution d'acide chloroaurique par la méthode des piles à électrodes de dissolution.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370143
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  • 63
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    Neue Synthese des 3-Desoxy-4,6-benzyliden-α-methyl-D-glucopyranosids (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 378-381 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Es wird eine neue Darstellung des 3-Desoxy-4, 6-benzyliden-α-methyl-D-glucopyranosids (II) durch Reduktion von 2,3-Ditosyl-4,6-benzyliden-α-methyl-D-glucopyranosid (I) durch Lithiumaluminium hydrid beschrieben.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370147
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  • 64
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    Recherches sur l'autoxydation des aldéhydes. I. Applications de la spectrographie infrarouge; mise en évidence d'un composé intermédiaire (moloxyde) (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 345-359 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: En étudiant spectrographiquement l'autoxydation de l'aldéhyde benzoïque, nous avons mis en évidence une bande nouvelle, de fréquence 1270 cm-1, se repportant à un produit intermèdiaire, formé avant l'acide perbenzoïque.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370144
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  • 65
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    Theorie der Form von Absorptionsbanden suspendierter Substanzen und deren Anwendung auf die Nujolmethode in der Infrarotspektroskopie (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 360-374 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Für optisch weiche Kugeln wurden Streuung und Absorption elektromagnetischer Wellen in der Gegend einer Spektrallinie theoretisch untersucht. Die sich aus der Theorie ergebenden merkwürdigen Veränderungen der Transmissionskurven wurden an zahlreichen Beispielen diskutiert.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370145
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  • 66
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    Eine Synthese des Pantethins (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 375-377 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die in einer früheren vorläufigen Mitteilung erwähnte neue Pantethin-Synthese wird ausführlich beschrieben. Von dem Pantethin konnte ein cyclisch gebauter Phosphorsäureester dargestellt werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370146
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  • 67
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    Über die Vitamin-A-Wirkung des cis-β-Carotins C (mit behinderter Doppelbindung) (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 382-382 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370148
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  • 68
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    Reaktionen mit 15N. XI. Zur Bildung von Phenylazid aus Phenyldiazoniumperbromid und Ammoniak (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 383-388 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Es wird mit Hilfe von 15N gezeigt, dass bei der Bildung von Phenylazid aus Phenyldiazoniumperbromid und Wässeriger Ammonialklösung die Stickstoffatome streng nach dem Brutto-Schema aneinandergefügt werden. Nur die lineare Struktur ist verträglich mit den Analysenergebnissen, die zugleich einen Beweis für die Zuverlässigkeit der schon früher benutzten Abbaureaktionen des Phenylazids erbringen.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370149
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  • 69
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    Synthese von freiem 11-Epi-corticosteron über 11α-Trifluoracetate. Bestandteile der Nebennierenrinde und verwandte Stoffe, 87. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 388-393 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die Teilsynthese von 11-Epi-cortiocosteron unter Verwendung von Trifluoressigsäure-estern als Zwischenprodukten wird beschrieben.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370150
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  • 70
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    Verzeichnis der im Tauschverkehr eingehenden Zeitschriften. (Stand 31. XII. 1953) (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 394-396 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370152
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  • 71
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    Masthead (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954) 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370201
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  • 72
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    Bei der Redaktion eingelaufene Bücher: (Die Redaktion verpflichtet sich nicht zur Besprechung der eingesandten Werke.) (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 393-393 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370151
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  • 73
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    Synthesen einiger Piperidin-methyl-Homologen (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 397-402 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Aus Di- und Trimethyl-glutarsäuren, die z. T. nach verbesserten bekannten Methoden gewonnen wurden, hat man die entsprechenden Di- und Trimethyl-glutarsäure-anhydride und -imide hergestellt und letztere mittels LiAlH, in folgende Piperidin-methyl-Homologen uber- geführt : 3,5-Dimethyl-piperidin, 4,4-Dimethyl-piperidin, 3,S-Dimethyl-piperidin, 3,3,5-Trimethyl-piperidin und 3,4,4-Trimethyl-piperidin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370202
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  • 74
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    Die Glykoside der Samen von Acokanthera friesiorum Markgr. Glykoside und Aglykone, 124. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 403-427 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die Isolierung der wichtigsten Glykoside der Samen von Acokanthera friesiorum Markgr. aus Kenya wird beschrieben. Die Samen enthielten als Hauptkomponente ca. 1,7 % des bekannten Acovenosid A. Daneben liessen sich aber auch etwa 0,l% Ouabain isolieren sowie kleine Mengen von Acolongiflorosid E, Acolongiflorosid G, Acolongiflorosid H, Acolongiflorosid-K-Acetat und ein Kristallisat, das als „Kristallisat Nr. 4“ bezeichnet wird und das ein Gemisch dar-stellt. Durch Verteilungschromatographie liess es sich in 3 Komponenten zerlegen, von denen eine rnit Acolongiflorosid E identisch war, während die zwei anderen neue Glykoside darstellten, die als Acofriosid L und Acofriosid M bezeichnet werden. - Fur einen Abbau war nicht genügend von diesen zwei Stoffen in reiner Form vorhanden, hingegen wurde die Spaltung von „Kristallisat Nr. 4“ mit HClin Aceton durchgeführt. Das in diesem Gemisch erhaltene Acolongiflorosid E blieb dabei weitgehend unverändert. Als Spaltprodukte wurden ein neuer krist. Zucker erhalten, den wir Acofriose (V) nennen, sowie 3,5-Dianhydro-periplogenin (VI), das sich zum Vergleich auch teilsynthetisch aus Periplogenin bereiten liess. Wir vermuten, dass diese zwei Spaltstücke aus Acofriosid L stammen, so dass sich fur dieses Glykosid eine Teilformel aufstellen liess.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370203
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    H. E. Fierz-David 1882-1953 (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 427-435 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370204
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  • 76
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    Dérivés de l'aldéhyde nitro-4-salicylique. 1re communication: la nitro-6-coumarone (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 435-436 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The synthesis of 6-nitrocoumarone via 6-nitrocoumarilic acid has been described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370205
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    Dérivés de l'aldéhyde nitro-4-salicylique. 2e communication. Le chlorhydrate de l'amino-6-coumarone et quelques composés organiques fournissant des complexes chélatés avec des ions de métaux lourds (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 437-443 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The preparation of 6-amino-coumarone hydrochloride has been described. The antitubercular activity of some isonicotinoylhydrazones (somewhat more active against INH-resistent strains of Myc. tuberculosis than INH) and of different compounds liable to form metal complexes has been shown.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370206
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  • 78
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    Synthesen von 11β-Oxy-corticoiden über die 11β-Formyloxy- und 11β-Trifluoracetoxy-Derivate. Bestandteile der Nebennierenrinde und verwandte Stoffe, 88. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 443-450 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die Synthese von 3β,21-Diacetoxy-11β-oxy-allopregnanon-(20) und von Corticosteron-21-monoacetat, ausgehend von entsprechenden Ätiansäuren, wird beschrieben. Als Zwischenprodukte waren Stoffe, bei denen die 11β-Oxygruppe mit Ameisensäure oder mit Trifluor-essigsäure verestert war, geeignet.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370207
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  • 79
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    Über die Glykoside von Bowiea volubilis Harvey. 5. Mitteilung. Glykoside und Aglykone, 130. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 451-454 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Aus den Zwiebeln von Bowiea volubilis Harvey wurde eine weitere, vorläufig Bowieasubstanz G genannte Substanz isoliert. Es wurde daraus das mit NaBH4 erhältliche Reduktionsprodukt und dessen Acetat hergestellt. Es wird vermutet, dass das Aglykon von Bovosid A vorliegt; der strenge Beweis dafür steht aber noch aus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370208
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  • 80
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    Über Derivate des Iminodibenzyls (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 472-483 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 1. Es wird die Darstellung von aminoalkylierten und aminoacylierten Derivaten des Iminodibenzyls (10, 11-Dihydro-5-dibenzo-[b, f]-azepin) beschrieben.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370211
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  • 81
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    Electronic Resource
    Synthesen von substituierten Tropinderivaten (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 484-494 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Es werden Synthesen des 2,5-Dimethoxy-3-oxy-4-chlortetrahydro-furans (I), 2,3,5-Trimethoxy-tetrahydro-furans (IV), 2,3,4,5-Tetramethoxy-tetrahydro-furans (X), 6,7-Dimethoxy-tropinons (XIIIa,XIIIb), 6-Methoxy-tropinons (XIIa,XIIb), 1-Methoxymethyltropinons (XVIII, R = CH2OCH3), 1-Methoxymethyl-tropins (XIX, R=CH2OCH3, R′=H), 1-Methoxymethyl-pseudotropins (XX,R=CH2OCH3, R′=H), 1-Methoxymethyl-tropacocains (XX, R=CH2OCH3, R′=COC6H5), 1-Oxymethyl-tropinons (XVIII, R=CH2OH), 1-Oxymethyl-tropins (XIX, R=CH2OH, R′=H), 1-Acetoxy-methyl-tropinons (XVIII, R=CH2OCOCH3), 1-Acetoxy-methyl-tropins (XIX, R=CH2OCOCH3, R′=H), 1-Carboxy-tropinons (XVIII, R=COOH) und des 1-Carbomethoxy-tropinons (XXIII) beschrieben und die Konfiguration bzw. Konformation der erwähnten Tropinon- und Tropinderivate diskutiert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370212
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  • 82
    Electronic Resource
    Electronic Resource
    Etude polarographique de la salive (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 455-461 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Diluted human saliva in an ammonia buffer solution and in presence of CoII gives three catalytic waves, whilst blood serum, under the same conditions, gives only two waves. Saliva presents the first two waves only in the presence of CoII, but the third wave appears in buffer solution with or without CoII. After denaturation with potassium hydroxyde under the given conditions the third wave disappears completely, whilst the first and the second waves augment. Saliva changes its properties when kept; the stability of the waves is diminished in regressive order from h, to h,. After simple dialysis the second and third waves disappear, whilst the first wave does not change. After electrodialysis during two and a half hours, the first wave disappears, but the third wave is hardly changed. The water used for the simple dialysis has also been examined under the polarograph; this gave only the second and the third waves, but the behaviour of the third wave with or without CoII is quite different from the behaviour of h, taken from a saliva which has not been dialysed. By addition of cystine or cysteine to the saliva, the third wave increases when CoII is present, but it decreases in the absence of this ion.
    Additional Material: 5 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370209
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  • 83
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    Die Glykoside von Carissa ovata (R. Brown) var. stolonifera F. M. Bailey und Carissa lanceolata (R. Brown) (Apocynaceae). Glykoside und Aglykone, 125. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 462-471 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Aus den Wurzeln von Carissa ovata (R. Br.) var. stolonifera F. M. Bailey aus Westqueensland (Australien) liessen sich nach wiederholter Chromatographie ca. 0,0007% eines krist. Glykosids gewinnen, das höchst wahrscheinlich mit Odorosid H identisch ist. Andere Glykoside liessen sich auch papierchromatographisch nicht nachweisen. - Zweige und Blätter wurden nur qualitativ geprüft und enthielten sicher nicht mehr als Spuren digitaloider Glykoside.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370210
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  • 84
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    Electronic Resource
    Über Synthesen von neuartigen Verbindungen aus der 6-Alkoxy-tropan-Reihe. 5. Mitteilung über Alkaloid-Synthesen (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 495-510 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Wir berichten über die Fortsetzung unserer Untersuchungen auf dem Gebiet der 6-Alkoxy-tropane, die sich auf den 2,5-Dialkoxy- bzw. 2,5-Diacyloxy-3-oxy-4halogen-tetrahydro-furanen und andern Furanderivaten als Schlüsselsubstanzen aufbauen. Letztere führten seinerzeit zu den entsprechenden O-Alkyl-äpfelsäure-dialdehyden. Durch Kondensation dieser Dialdehyde mit primären aliphatischen Aminen und Acetondicarbonsäure sind in der vorliegenden Arbeit eine grössere Zahl von 6-Alkoxy-tropinonen aufgebaut worden (siehe Tabelle 1).
    Additional Material: 4 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370213
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  • 85
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    Heilmittelchemische Studien in der heterocyclischen Reihe. 6. Mitteilung. Pyridazine III. Derivate des cyclischen Maleinsäure- und Citraconsäure-phenylhydrazids (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 510-523 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The reaction of phenylhydrazine with maleic acid anhydride and with citraconic acid anhydride was studied. The cyclic phenylhydrazides (1-phenyl-3-hydroxy-6-pyridazones) obtained in this way served as starting materials for the preparation of substituted 1-phenyl-6-pyridazones. Some of them show analgesic and antipyretic activity.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370214
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  • 86
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    Heilmittelchemische Studien in der heterocyclischen Reihe. 7. Mitteilung. Pyridazine IV. Derivate des cyclischen Chlormaleinsäure-phenylhydrazids (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 523-533 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The reaction between chloromaleic acid anhydride and phenylhydrazine is studied. The constitution of the two isomeric 1-phenyl-3-hydroxy-chloro-pyridazones-(6) is established. Starting with 1-phenyl-3-hydroxy-4-chloro-pyridazone-(6) some derivatives are prepared. Some of them show good analgesic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370215
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  • 87
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    Zur Kenntnis der Sesquiterpene und Azulene. 109. Mitteilung. Über stereoisomere Bicyclo-[0, 3, 5]-decan-8-ole und deren Wasserabspaltungsprodukte (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 534-542 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Durch Destillation der Produkte der katalytischen Hydrierung von Δ1,7-Bicyclo-[0,3,5]-decen-8-on (I) konnten neben dem Kohlenwasserstoff cis-Bicyclo-[0,3,5]-decan (IV) und dem cis-Bicyclo-[0,3,5]-decan-8-on (II) die beiden stereoisomeren Alkohole cis-Bicyclo-[0,3,5]-decan-trans-8-ol (IIIa) und cis-Bicyclo-[0,3,5]-decan-cis-8-ol (IIIb) in reiner Form isoliert werden. Auf Grund von physikalischen und chemischen Eigenschaften wird die Stereochemie dieser Verbindungen diskutiert.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370216
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  • 88
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    Zur Kenntnis der Diterpene. 65. Mitteilung. Über einen Ambrariechstoff aus Manool (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 543-546 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Beim oxydativen Abbau von Manool (I) mit Kaliumpermanganat entsteht neben dem bereits beschriebenen Methyl-keton C18H30O (II) eine neutrale Verbindung C18H30O2, welche die Konstitution eines intramolekularen Acetals IV besitzt. Die Verbindung IV weist einen starken, dauerhaften und angenehmen Ambrageruch auf, der auf die intramolekulare Acetal-Gruppierung zurückzuführen ist.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370217
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  • 89
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    Über Steroide und Sexualhormone. 199 Mitteilung. Über die direkte konfigurative Verknüpfung der Steroide mit dem Citronellal, ein Beitrag zur Bestimmung der absoluten Konfiguration der Steroide (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 546-552 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: In dieser Arbeit ist es gelungen, die Steroide mit Hilfe von direkten Umwandlungen mit den Monoterpenen konfigurativ zu verknüpfen. Daraus ergibt sich, dass die gebräuchlichen Projektionsformeln der Steroide Korrekt sind und ihre absolute Konfiguration wiedergeben.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370218
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  • 90
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    Electronic Resource
    Über die Hydrogenolyse von α- und β-Menaphtylamin-Derivaten. 4. Mitteilung über Hydrogenolyse (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 565-574 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Bei der konkurrierenden Hydrogenolyse von Aminen wird die α-Menaphtylgruppe etwas leichter abgespalten als die β-Menaphtyl-gruppe.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370220
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  • 91
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    Electronic Resource
    Zur Kenntnis des Fluorocurins. 10 Mitteilung über Curarealkaloide aus Calebassen (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 553-565 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Aus dem Calebassen-alkaloid Fluorocurin C20H25O2N2⊕, einem Indoxylderivat, wurde durch Reduktion mit NaBH4 Hydro-fluorocurin C20H27O2N2⊕ erhalten, welches durch Säuren sehr leicht in das Indolderivat Mavacurin C20H25ON2⊕ übergeht. Mavacurin, ein Calebassen-alkaloid, haben wir auch in Rinde von Strychnos toxifera gefunden. Die Überführung von Fluorocurin in Mavacurin gelang auch direkt durch Reduktion ersterer Verbindung mit Zink und Schwefelsäure. Durch thermische Spaltung wurde Fluorocurin in Norfluorocurin C19H22O2N2 übergeführt; letzteres lässt sich durch Reduktion mit NaBH4 oder LiAlH4 in Norhydro-fluorocurin C19H24O2N2 verwandeln, das seinerseits durch Methylierung in Hydro-fluorocurin C20H27O2N2⊕ und durch H-Ionen in Normavacurin C19H22ON2 übergeht. Methylierung des Normavacurins liefert Mavacurin.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370219
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  • 92
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    Electronic Resource
    Zur Kenntnis der Zucker-osazone. 5 Mitteilung. Abbau von vier 3,6-Anhydro-hexose-phenylosotriazolen zu kristallisierten antipoden Dialdehyd-hydraten (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 574-583 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Vier 3,6-Anhydro-hexose-phenylosotriazole, die aus Diels'schen Anhydro-hexose-phenylosazonen zugänglich sind, wurden mit Perjodsäure oxydiert. Als Oxydationsprodukte wurden optisch aktive Dialdehyd-hydrate in antipoden Formen und in kristallisiertem Zustand isoliert. Die Dialdehyd-hydrate, deren Konstitution durch Derivate und Abbauprodukte gesichert wurde, ermöglichten auf einfachstem Wege eine konfigurative Verknüpfung des asymmetrischen C-Atoms 3 der 3,6-Anhydro-triazole und bestätigten unsere früheren Konfigurationsbestimmungen. Acetylierung der Dialdehyd-hydrate führte unter Aufhebung der Asymmetrie ohne Verlust von C-Atomen zu einem für sämtliche 3,6-Anhydro-hexose-phenyloso-triazole gemeinsamen Monoacetyl-Derivat, für welches eine Acetoxy-1,4-dioxen-Struktur weitgehend bewiesen wurde.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370221
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  • 93
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    Zur Kenntnis der natürlichen Konvektion bei der Elektrolyse: Interferometrische Untersuchungen der Diffusionsschicht I (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 583-597 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An interferometric method for the study of cathode films in electrolytic baths is described. It is based on the principle of the Jamin interferometer, with a cylindrical lens for focusing the cell.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370222
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  • 94
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    Sur le dosage volumétrique du fluor (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 598-602 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A simple and accurate volumetric method for the determination of fluorine is described. The titration is carried out in 50% methanol solution, using standard cerous chloride solution as titrant and murexide as indicator. Stoichiometric results are obtained with solutions containing 1 to 10 mg F. The method is suitable for titrating the distillates collected in the Willard-Winter steam distillation of fluosilicic acid.
    Additional Material: 2 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370223
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  • 95
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    Die Ionisationskonstante von Nicotinsäureamid in wässeriger Lösung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 602-606 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: UV spectra of nicotinamide in dilute aqueous solutions of hydrochloric acid (4 · 10-4-m. -0,1-m.) and in alkaline solution were mea-sured at 20°. The ionisation constants of nicotinamide for different ionic strengths were calculated from the experimental data. The ionic strength was varied by addition of potassium chloride. Linear extra-polation of pK to zero ionic strength gave a value of pK0=3,328 (± 0,010) for the thermodynamic ionisation exponent at 20°.
    Additional Material: 1 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370224
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  • 96
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    Contribution à l'étude du système quinaire Ca++—NH4+—H+—NO3-—PO4---—H2O. XII. Le système quaternaire Ca++—H+—NO3-—PO4---—H2O à 25° (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 607-619 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 1. Nous communiquons les résultats de 105 déterminations de solubilité concernant le systéme quaternaire \documentclass{article}\pagestyle{empty}\begin{document}$$ {\rm Ca}^{{\rm + + }}\,{\!-\!-}\,{\rm H}^{\rm + }\,{\!-\!-}\,{\rm NO}_{\rm 3} ^ - - {\rm PO}_{\rm 4} ^{ - - - }\,{\!-\!-}\,{\rm H}_{\rm 2} {\rm O} $$\end{document} á 250°.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370225
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  • 97
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    Recherches sur le spectre d'absorption infrarouge des ozonides. VIII. Détermination des spectres des ozonides de quelques esters comportant une double liaison éthylénique: acrylate d'éthyle, méthacrylate de méthyle, chloracrylate de méthyle, fumarate de méthyle et cinnamate d'éthyle (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 620-626 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Nous avons attiré l'attention sur une particularité des ozonides d'esters, soit l'attention et même la suppression de la bande caractéristique du groupe C=O de l'ester. Il ya lieu d'associer cette constatation á la présence ou á l'absence d'un hydrogéne en position α par rapport au carboxyle estérifié.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370226
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  • 98
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    Recherches sur l'autoxydation des aldéhydes. II. Etude thermochimique de l'autoxydation de l'aldéhyde benzoïque (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 626-635 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Le but de ces recherches a été de déterminer les énergies mises enjeu dans les trois processus successifs suivants, caractérisant la marche de l'autoxydation, telle qu'elle a pu être établie par la spectrographie d'absorption infrarouge (voir le mémoire précédent) : formation d'un corps intermédiaire, le moloxyde, isomérisation du moloxyde en per-acide, et réaction du peracide sur l'aldéhyde, aboutissant á l'acide.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370227
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  • 99
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    Metallionen und Resistenzbildung bei Tbc-Kulturen. Metallionen und biologische Wirkung, 22. Mitteilung (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 636-641 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Die tuberkulostatische Aktivität von Picolinsäure-hydrazid und Thiazol-2-carbonsäurehydrazid und ihre Beeinflussbarkeit durch Thiophen-2-carbonsäurehydrazid und Cu‥ wird angegeben, und ein zur Resistenzbildung führender Mechanismus wird diskutiert.
    Additional Material: 1 Tab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370228
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  • 100
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    Über den Abbau der Harnsäure zur Oxonsäure (Allantoxansäure) (1954)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 37 (1954), S. 641-644 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Using isotopic tracer methods, we have established which C and N atoms of the uric acid molecule are incorporated into oxonic acid (allantoxanic acid) and allantoxaidine. These two alkaline oxidation products do not contain the original imidazole ring of uric acid. Symmetrical triazine structures are proposed to replace the generally accepted imidazolidine formulas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19540370229
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