Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Disposition of β-methyldigoxin in man (1975)
    Springer
    European journal of clinical pharmacology 9 (1975), S. 105-114 
    Details
    ISSN: 1432-1041
    Keywords: Methyldigoxin ; excretion ; deep compartment ; O-demethylation ; glycosides ; metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The time course of radioactivity in plasma and the excretion in urine and faeces over 7 days were determined in 12 healthy subjects after single oral and intravenous doses of a solution of3H-β-methyldigoxin. 62.2±2.1 and 29.0±5.2 per cent of the dose were excreted in urine and faeces, respectively, within 7 days of intravenous administration, compared with 55.2±2.8 and 28.6±5.7 per cent after oral administration. This indicates almost complete absorption of the glycoside when given in solution. 12 hours after its administration a pseudo-distribution equilibrium was reached and the average half life of tritiated compounds was 1.3 days. By 48 – 96 hours after treatment the average half life was 2.8 days. O-demethylation was revealed as the main metabolic degradation step in man. The rate of Demethylation was higher after oral than i.v. administration. Thus, only 31% of the radioactivity excreted in the urine consisted of unchanged β-methyldigoxin after oral administration compared to 51% after i.v. dosing. Only traces of bis- and monoglycosides were excreted in urine, but there were considerable amounts in faeces, where they accounted for more than 35% of the total excretion. Up to 40% of the radioactivity in plasma and urine consisted of polar conjugates during the first 12 hours after administration of β-methyldigoxin. The mono- and bisglycosides were identified as the main products of conjugation. During the 7 days approximately 15% of the administered dose was metabolized by splitting off glycosidic bonds and conjugation to polar compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614005
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Disposition kinetics of spironolactone in hepatic failure after single doses and prolonged treatment (1977)
    Springer
    European journal of clinical pharmacology 11 (1977), S. 169-176 
    Details
    ISSN: 1432-1041
    Keywords: Spironolactone pharmacokinetics ; tritiated metabolites ; fluorigenic metabolites ; decompensated liver disease ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Six male patients with histologically characterised, decompensated liver disease who had not previously received spironolactone, were given orally Aldactone® 7 mg/kg with3H-spironolactone 100 µCi. The kinetics of the drug were studied in plasma and urine for 6 days. Then, Aldactone® 7 mg/kg was given daily for 12 consecutive days, and the pharmacokinetics of a single dose of3H-spironolactone were re-examined. The kinetics of total radioactivity, as well as of fluorigenic metabolites in plasma, after the first single dose of spironolactone did not differ in patients and normal test subjects; similar percentages of the dose given were excreted within 6 days in urine from patients (47.47±4.88%) and from controls (53.68±2.04%). The kinetics of CH2Cl2/H2O distribution coefficients of labelled material in plasma and urine, as well as TLC analysis of the CH2Cl2 soluble fraction, revealed no significant differences from controls. After treatment for 12 days with spironolactone, 4 out of 6 patients showed marked acceleration in the rate of elimination of radioactivity from plasma and a corresponding increase in excretion of labelled compounds in urine. Analysis of the excretion products in urine revealed proportionally increased excretion and no evidence of selective induction of a single degradation step. In contrast, delayed elimination was observed in the 2 other patients after 12 days' treatment. However, this was due to dehydration and oliguria caused by over-treatment with the diuretic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606406
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    ISolation and identification of a sulfur-containing metabolite of spironolactone from human urine
    Amsterdam : Elsevier
    Steroids 28 (1976), S. 467-480 
    Details
    ISSN: 0039-128X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0039-128X(76)90016-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of spironolactone in man (1976)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 296 (1976), S. 37-45 
    Details
    ISSN: 1432-1912
    Keywords: Spironolactone ; Pharmacokinetics ; Metabolic pathways ; Urinary and fecal excretion ; Fluorigenic metabolites ; Tritiated metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five healthy male volunteers received 500 mg Aldactone® orally together with 100 μCi 3H-20-21-spironolactone; one elderly patient received 1 mCi 3H-spironolactone without additional ‘cold’ drug. For 6 days the disposition kinetics of the drug were studied in plasma, urine and feces. The tritium concentrations in plasma reached a peak between 25–40 min after administration amounting to 2–3% of the dose/1. Up to the 12th h, they fell rapidly and showed a monoexponential decline (t 1/2 : 2.57±0.27 days) between the 36th and 96th h. Later, a striking increase in the speed of elimination of radioactivity from plasma (t 1/2 : 1.66±0.21 days) was observed. The biological half-life of labeled material in plasma was longer than that of fluorigenic compounds. 47–57% of the dose were excreted in urine and the remaining amount culd be detected in feces (total recovery 90%). The half-life of the urinary excretion rate was distinctly shorter (t 1/2 : 0.9±0.11 days) than that of total radioactivity in plasma. This, together with an observed increase of the polar fraction in urine from 35 up to 85%, which was accompanied by a decrease in plasma from 55 to 35%, suggests either tubular reabsorption or enterohepatic recirculation of lipophilic compounds. TLC-separation of the lipophilic fraction in urine revealed two previously unknown compounds of which the main congener was identified as 3-(3-oxo-7α-methylsulfonyl-6β, 17β-dihydroxy-4-androsten-17α-yl) propionic acid γ-lactone, as well as canrenone and the metabolites which have already been described (Karim and Brown, 1972; Karim et al., 1975). This metabolite represents the main lipophilic degradation product in urine within the first hours, whereas the 6β-OH-7α-methylsulfinylspirolactone leveled off and seemed to be an endexcretion product. For further characterisation, the polar fraction was subjected to acidic hydrolysis. The known metabolic pathways of spironolactone degradation are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498838
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Formation and disposition of bis- and monoglycosides after administration of3H-4‴-methyldigoxin to man (1974)
    Springer
    European journal of clinical pharmacology 7 (1974), S. 177-181 
    Details
    ISSN: 1432-1041
    Keywords: Digoxin ; 4‴-methyldigoxin ; bis- and monodigitoxosides ; polar conjugates ; biliary excretion ; faecal degradation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The metabolites of tritiated 4‴-methyldigoxin (MD) has been studied in bile, urine and faeces from 3 patients 24 h after cholecystectomy and T-tube drainage. 5.6–15.6% of the doses were eliminated in bile and 28.5–57.8% in urine within 48 h. In bile after 6 h, approximately 5% of the excreted products were bisglycosides (B) and only traces were monoglycosides (M), whereas 55.3±4.5% were CHCl3-insoluble metabolites. At the same time urine contained 15.5±1.3% CHCl3-insoluble compounds. Anaerobic incubation of bile with a stool suspension (SS) decreased the polar fraction by 64.8±4.5% (n=6); incubation with a previously autoclaved SS decreased it only by 12.7±2.7%. Preincubation of SS with carbenicillin, cephalotin and ampicillin to depress bacterial growth largely suppressed the metabolic activity. TLC-analysis revealed that the decrease in the polar fraction corresponded to an increase of M, whilst MD, digoxin and B were almost unaltered. The results imply that B and M were formed in the liver, B was preferentially eliminated unchanged in bile and M was conjugated to CHCl3-insoluble compounds prior to excretion. The polar conjugates were split by bacterial enzymes in the colon to yield M, which could be detected in faeces.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00560378
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Demethylation and cleavage of glycosidic bonds of 4‴-methyldigoxin in man (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 272 (1972), S. 450-453 
    Details
    ISSN: 1432-1912
    Keywords: Urinary Excretion ; Methyldigoxin ; Digoxin ; Metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In man the oral or intravenous administration of 4‴-methyldigoxin yields metabolites in urine which are soluble either in chloroform or in water. The chromatographic analysis reveals demethylation as the main metabolic reaction in man. In addition to methyldigoxin and digoxin small amounts of digoxigenin-bisdigitoxoside and digoxigenin-mono-digitoxoside can be detected. The water soluble metabolites represent 7% of the radioactivity excreted in 7 days reaching a maximum within the first 8 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501252
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetic behaviour of 4‴-methyldigoxin in man (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 273 (1972), S. 172-174 
    Details
    ISSN: 1432-1912
    Keywords: 4′-Methyldigoxin ; Half Life ; Excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 10 patients the time course of specific activity in plasma, and the excretion rates in urine and feces after oral and intravenous administration of 12α-3H-4‴-methyldigoxin were studied. The determined biological half life of radioactivity in plasma averaged 43 h and corresponds with the renal excretion velocity (50 h). 32.5 ± 5.0 and 31.5 ± 6.3% of the dose were found in feces and 59.7 ± 1.3 and 52.9 ± 1.8% were excreted in urine within 7 days after intravenous and oral administration, respectively. These results together with the observed plasma concentrations suggest a rapid and almost complete absorption of 4′-methyldigoxin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508089
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    Effect of enterohepatic circulation on the pharmacokinetics of spironolactone in man (1977)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 300 (1977), S. 281-287 
    Details
    ISSN: 1432-1912
    Keywords: Spironolactone ; Pharmacokinetics ; Enterohepatic circulation ; Urinary excretion ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 100 μCi 3H-spironolactone together with 300 mg unlabeled drug were administered orally to 8 patients, 24 h after choledochotomy with subsequent complete drainage of bile for a further 96 h by means of a special tube. To evaluate the role of entero-hepatic circulation, the excretion of tritiated substances in bile was investigated and their kinetics in plasma and urine were compared with that of controls. The 3H-activity in plasma declined monoexponentially with t 1/2: 1.80±0.12 d from 12 h after patients received the drug. This half life was not different from that of controls in the terminal slope, 96–144 h after administration. However, between 24–96 h the elimination was significantly delayed (t 1/2: 2.79±0.29 d) in controls. This was the result of entero-hepatic cycling of spironolactone metabolites with high biliary clearance. 5.4–32.7% of the dose was excreted in bile within 4 days; of this 50–70% consisted of polar material, 10–20% of canrenone, 5–15% of 6β-OH-7α-methylsulfinyl-spirolactone and 3–10% of 6β-OH-7α-thiomethyl-spirolactone. In urine, identical percentages of the dose were excreted in patients and controls. TLC-examination of the lipophilic fraction revealed less sulfoxidized metabolites while, at the same time, significantly higher amounts of 6β-OH-7α-thiomethylspirolactone and canrenone were eliminated in patients with biliary fistula. Thus, interruption of enterohepatic circulation had resulted in a shift of metabolic pathways of this drug in spite of an unchanged overall metabolic rate. Furthermore, the experiments allow a logical interpretation of the kinetics of 3H-activity in plasma after administration of 3H-spironolactone in normal man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500971
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Effects of pretreatment with spironolactone on pharmacokinetics of 4‴-methyldigoxin in man (1976)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 292 (1976), S. 87-92 
    Details
    ISSN: 1432-1912
    Keywords: Spironolactone ; 4‴-Methyldigoxin ; Half life in plasma ; Biliary, faecal and renal excretion ; Metabolism ; Clinical pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pharmacokinetics of 3H-4‴-methyldigoxin (md) were studied in three paired experiments with and without pretreatment with spironolactone (7 mg/kg/day for 7 days) and in one additional test person after pretreatment only. The results were compared with controls after oral (n=6) and intravenous (n=6) administration of md. In addition the biliary excretion of md and its metabolites was investigated in biliary fistula patients with and without pretreatment with spironolactone. After pretreatment of normal persons maximum plasma levels of tritium were approximately 35% lower and they were reached on average 60 min after oral administration as compared with approximately 15 min without pretreatment. Already 12 hrs after oral administration the plasma concentrations, with and without pretreatment, no longer differed and the biological half lives of radioactivity in plasma were equal. With or without pretreatment, the cumulative excretion of tritium in urine and faeces was nearly identical in the paired experiments within 7 days. It was in the range of the controls which eliminated 55.2±2.8 and 28.6±5.7% of the dose in urine and faeces, respectively, after oral, and 62.2±2.1 and 28.9±5.2%, respectively, after i.v. administration. Accordingly after pretreatment the radioactivity excreted in bile within 48 hrs (14.9% of the dose) did not differ from controls. Examination of the composition of labelled compounds excreted in urine and bile revealed no significant alterations in the metabolic degradation of md under the influence of spironolactone. Thus the profound effects of spironolactone upon pharmacokinetics of md previously observed in rats are without any significance for human conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00506494
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...