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
