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  • 1
    Electronic Resource
    Electronic Resource
    Twenty-four-hour intragastric pH profiles and pharmacokinetics following single and repeated oral administration of the proton pump inhibitor pantoprazole in comparison to omeprazole. (1996)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 10 (1996), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: BACKGROUND: Pantoprazole is a proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzyme system in man. Its effect on intragastric pH following single and repeated oral intake was investigated in comparison to omeprazole by continuous intragastric pH-metry at doses recommended for treatment of peptic ulcer disease. METHODS: Sixteen healthy male subjects underwent two dosing periods. From day 1 to day 7, they were given once daily by mouth 40 mg pantoprazole in one period and 20 mg omeprazole in the other period, according to a double-blind randomized crossover design. Twenty-four-hour intragastric pH was recorded and frequent blood samples for pharmacokinetic analysis were taken on day 1 and day 7. A placebo pH profile was obtained prior to each treatment period. RESULTS: Pantoprazole was significantly more effective than omeprazole with regard to increase in 24-h and daytime pH, following both single (median 24-h pH: 1.45 vs. 1.3, P 〈 0.05; median daytime pH: 1.6 vs. 1.3, P 〈 0.01) and repeated (median 24-h pH: 3.15 vs. 2.05, P 〈 0.01; median daytime pH: 3.8 vs. 2.65, P 〈 0.05) oral intake. As compared to the first dose, repeated administration of both drugs markedly increased the effect on intragastric pH. With pantoprazole, steady- state serum concentrations were obtained after the first dose, but not with omeprazole. Both drugs were well tolerated without relevant changes in vital signs of clinical laboratory parameters. CONCLUSION: Pantoprazole 40 mg is significantly more effective than omeprazole 20 mg in raising intragastric pH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0953-0673.1996.00359.x
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  • 2
    Electronic Resource
    Electronic Resource
    Tolerance, safety, and kinetics of the new antineoplastic compound dexniguldipine-HCl after oral administration: a phase I dose-escalation trial (1995)
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 160-164 
    Details
    ISSN: 1432-0843
    Keywords: Dexniguldipine-HCl ; Phase I trial ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dexniguldipine-HCl is a new dihydropyridine compound that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. The purpose of this trial was to determine the toxicity and pharmacokinetics of dexniguldipine and to establish a recommended dose for phase II trials. A total of 37 patients with cancer were treated with oral dexniguldipine in increasing doses for up to 7 days. The main parameters evaluated were subjective tolerance and laboratory and cardiovascular parameters (blood pressure and ECG). Blood samples were drawn for analysis of the drug's pharmacokinetics. Dizziness and nausea were the major adverse events observed in seven patients, but episodes were generally mild and not clearly dose-related. Vomiting occurred in one patient. Hypotensive effects and orthostatic dysregulation were observed in some patients but were not considered to be dose-limiting. Therefore, no dose-limiting toxicity was found and the maximally tolerable dose could not be determined. Pharmacokinetic data showed wide interindividual variation and a dose-dependent increase in steady-state serum concentrations at doses of up to 1,000 mg daily, with no clear further increase being observed at higher doses. Consistently high concentrations were achieved with the 2,500-mg dose. Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetics properties of the compound; therefore, 2,500 mg/day is recommended as the daily dose for phase II trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689202
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  • 3
    Electronic Resource
    Electronic Resource
    Tolerance, safety, and kinetics of the new antineoplastic compound dexniguldipine-HCl after oral administration: a phase I dose-escalation trial (1995)
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 160-164 
    Details
    ISSN: 1432-0843
    Keywords: Key words Dexniguldipine-HCl ; Phase I trial ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Dexniguldipine-HCl is a new dihydropyridine compound that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. The purpose of this trial was to determine the toxicity and pharmacokinetics of dexniguldipine and to establish a recommended dose for phase II trials. A total of 37 patients with cancer were treated with oral dexniguldipine in increasing doses for up to 7 days. The main parameters evaluated were subjective tolerance and laboratory and cardiovascular parameters (blood pressure and ECG). Blood samples were drawn for analysis of the drug’s pharmacokinetics. Dizziness and nausea were the major adverse events observed in seven patients, but episodes were generally mild and not clearly dose-related. Vomiting occurred in one patient. Hypotensive effects and orthostatic dysregulation were observed in some patients but were not considered to be dose-limiting. Therefore, no dose-limiting toxicity was found and the maximally tolerable dose could not be determined. Pharmacokinetic data showed wide interindividual variation and a dose-dependent increase in steady-state serum concentrations at doses of up to 1,000 mg daily, with no clear further increase being observed at higher doses. Consistently high concentrations were achieved with the 2,500-mg dose. Despite the lack of dose-limiting toxicity, higher doses of dexniguldipine do not appear to be useful for clinical evaluation because of the pharmacokinetic properties of the compound; therefore, 2,500 mg/day is recommended as the daily dose for phase II trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00689202
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  • 4
    Electronic Resource
    Electronic Resource
    Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 277-281 
    Details
    ISSN: 1432-1041
    Keywords: Key words Pantoprazole; Proton pump inhibitor drug interaction ; oral anticoagulant phenprocoumon ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. Methods: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30–40% of normal within the first 5–9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11–15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. Results: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95–1.09), thus fulfilling predetermined bioequivalence criteria (0.70–1.43). The pharmacokinetic characteristics AUC0–24h and Cmax of S(−)-and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0–24h and of Cmax of S(−)-phenprocoumon (0.93, 0.87–1.00 for AUC0–24h; 0.95, 0.88–1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82–0.96; 0.9, 0.83–0.98) were within the accepted range of 0.8–1.25. Conclusion: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050198
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  • 5
    Electronic Resource
    Electronic Resource
    Antibacterial active components in human urine after administration of penicillins (1979)
    Springer
    Infection 7 (1979), S. 187-189 
    Details
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der 4-Stunden-Urin von freiwilligen Versuchspersonen und Patienten, die oral oder intravenös Penicilline erhalten hatten, wurde dünnschichtchromatographisch und mit Hilfe der Bioautographie untersucht. Bei nur zwei von 12 Penicillinen — Amoxicillin und Mezlocillin — waren keine antibakteriell aktiven Metaboliten nachzuweisen. Bei den übrigen Penicillinen besaßen diese unterschiedliche antibakterielle Aktivität, wie bei Verwendung verschiedener Testmikroorganismen gezeigt werden konnte. Nach Gabe von Carbenicillinestern wurden drei anti-bakteriell aktive Flecken getrennt, einer von ihnen entsprach dem Penicillin G; die beiden anderen besaßen Aktivität gegenüberPseudomonas aeruginosa. Das Bioautogramm nach Azlocillin-Therapie zeigte zwei Komponenten mit Aktivität gegenüberBacillus subtilis, Staphylococcus aureus undEscherichia coli; gegenüberP. aeruginosa jedoch war nur der schnell wandernde Fleck aktiv. Über die Bildung und die chemische Beschaffenheit dieser zusätzlichen aktiven Komponenten besteht noch weitgehend Unklarheit. Es ist jedoch durchaus möglich, daß sie die Bioverfügbarkeit eines Antibiotikums beeinträchtigen.
    Notes: Summary Four-hourly urine from volunteers and patients who had received penicillins orally or intravenously was investigated by means of thin layer chromatography and bioautography. Antibacterially active metabolites were not detected with only two of 12 penicillins, namely amoxicillin and mezlocillin. In the case of the other penicillins the metabolites possessed variable antibacterial activity as could be demonstrated using different test microorganisms. After administration of carbenicillin esters three antibacterially active spots were detected, one of which corresponded to penicillin G; the other two were active againstPseudomonas aeruginosa. The bioautogram after treatment with azlocillin showed two components which were active againstBacillus subtilis, Staphylococcus aureus andEscherichia coli; only the rapid moving component was active againstP. aeruginosa, however. The formation and chemical nature of these additional active components is still to a large extent not understood. It is quite possible, however, that they affect the bio-availability of an antibiotic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01640941
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  • 6
    Electronic Resource
    Electronic Resource
    A novel family of repeat sequences in the mouse genome responsive to retinoic acid (1996)
    Springer
    Mammalian genome 7 (1996), S. 741-748 
    Details
    ISSN: 1432-1777
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Repetitive DNA sequences form a substantial portion of eukaryotic genomes and exist as members of families that differ in copy number, length, and sequence. Various functions, including chromosomal integrity, gene regulation, and gene rearrangement have been ascribed to repetitive DNA. Although there is evidence that some repetitive sequences may participate in gene regulation, little is known about how their own expression may be regulated. During the course of gene trapping experiments with embryonic stem (ES) cells, we identified a novel class of expressed repetitive sequences in the mouse, using 5′ rapid amplification of cDNA ends-polymerase chain reaction (5′ RACE-PCR) to clone fusion transcripts from these lines. The expression of these repeats was induced by retinoic acid (RA) in cultured ES cells examined by Northern blot analyses. In vivo, their expression was spatially restricted in embryos and in the adult brain as determined by RNA in situ hybridization. We designated this family of sequences as Dr (developmentally regulated) repeats. The members of the Dr family, identified by cDNA cloning and through database search, are highly similar in sequence and show peculiar structural features. Our results suggest the expression of Dr-containing transcripts may be part of an ES cell differentiation program triggered by RA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003359900224
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