Relation between renal and hepatic excretion of drugs. XI. Excretion of sulfonamides with various physico-chemical properties of different ages--influence of nephrectomy or bile duct ligation.
The pharmacokinetics of a series of 6-sulfonamides, with gradually increasing molecular weights, were studied in anaesthetized rats after intravenous bolus injection. Immature (20-day-old) and adult (55-day-old) rats were compared. In both age groups renal excretion of all sulfonamides tested here dominates (about 5- to 10-fold). In 20-day-old rats renal and hepatic excretions are immature and reach about 50% (liver) or 30% (kidney) of adult values. Relation between renal and hepatic excretion of sulfonamides is strongly correlated to the lipophilicity of these substances. Hepatic excretion of sulfonamides seems to be correlated to their pKa-values. Concerning their excretion via urine it is necessary to correlate different steps of renal transport to physico-chemical properties in detail. A general correlation between renal excretion of sulfonamides and their chemical structure obviously does not exist. After bile duct ligation 24 h before clearance experiments no compensatory increase of renal sulfonamide excretion occurs. 24 h following bilateral nephrectomy hepatic excretion of sulfonamides is significantly enhanced; however, this phenomenon is related to physico-chemical properties of the sulfonamides. Age differences in compensation of one elimination pathway do not exist.
Fleck
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Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, G.D.R.
Nguyen
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Bräunlich
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D000375:Aging / Q000502:physiology; D000818:Animals; D001652:Bile Ducts / Q000503:physiopathology / Q000601:surgery; D005260:Female; D007668:Kidney / Q000378:metabolism* / Q000502:physiology; D008026:Ligation / Q000009:adverse effects; D008099:Liver / Q000378:metabolism* / Q000502:physiology; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000032:analysis / Q000378:metabolism*
D013449:Sulfonamides