Relation between renal and hepatic excretion of drugs: XV. Organ distribution and transport of the new antiarrhythmic drug Bonnecor in kidney and liver of rats.
Following administration of various doses of 14C-labeled Bonnecor (0.15 to 0.6 mg/100 g b.wt. i.v.) renal excretion of 14C-radioactivity dominates and the total rate of excretion both via kidney and liver reaches 60% during 6 h clearance experiment, independent of the administered dose. Otherwise nearly the same concentration of 14C-radioactivity can be measured in kidney and liver tissue. An alpha- und beta-slope of disappearance from the tissue seems to exist. At different times after administration of Bonnecor (0 to 15 h) the concentrations in kidney and liver tissue are distinctly higher compared with plasma concentrations. In vitro experiments on tissue slices confirm a nearly identical degree of accumulation of 14C-radioactivity in liver and kidney. In renal cortical slices the high degree of accumulation depends on active tubular transport processes. Comparing accumulation in liver slices under aerobic and anaerobic conditions a preferential passive uptake of Bonnecor can be demonstrated. Efflux kinetics in slices from liver and kidney cortex is in accordance with this interpretation.
Friedrich Schiller University Jena, Institute of Pharmacology and Toxicology, F.R.G.
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D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D001692:Biological Transport; D002250:Carbon Radioisotopes; D003984:Dibenzazepines / Q000493:pharmacokinetics*; D005260:Female; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000889:Anti-Arrhythmia Agents; D002250:Carbon Radioisotopes; D003984:Dibenzazepines; C048166:tiracizine