Relation between renal and hepatic excretion of drugs: XIII. Pharmacokinetics of new antiarrhythmic drug Bonnecor in rats with normal and impaired excretory functions

Experimental Pathology
C FleckH Bräunlich

Abstract

The clearance of 14C-Bonnecor, a weak organic cation, was measured in anaesthetized rats during 6 h after administration. The drug and its labelled metabolites are excreted both via kidney and liver. The renal excretion dominates especially following high doses. After bile duct ligation the renal excretion of Bonnecor increases significantly whereas in nephrectomized rats the biliary excretion of this substance is distinctly reduced. Plasma protein binding ratios amount to 60-70%. Renal removal of Bonnecor and the formed metabolites is in part a result of glomerular filtration. Increased urinary excretion of 14C-Bonnecor-activity under conditions of forced diuresis indicates the involvement of tubular reabsorption in renal handling of the drug and its metabolites. These in vivo results could be confirmed in experiments on renal cortical slices indicating a distinct tubular transport of the drug and its metabolites. In the kidney the aerobic accumulation of Bonnecor is very effective. Surprisingly, under anaerobic incubation conditions, uptake of Bonnecor into renal tissue remains relatively high indicating a distinct binding of Bonnecor within the tubular cells. In the liver the accumulation of Bonnecor is lower compared to the...Continue Reading

References

Jan 1, 1976·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P C HiromR L Smith
Jan 1, 1984·Experimental Pathology·M Hohenegger, H Schuh
Nov 1, 1982·Journal of Pharmaceutical Sciences·P J Basseches, G J DiGregorio

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Citations

Jul 1, 1996·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·A BarthW Klinger
Oct 1, 1992·Liver·C FleckH Bräunlich

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