Biliary excretion of synthetic benzamidine-type thrombin inhibitors in rabbits and rats.
In rabbits and rats the excretion via the bile of the highly effective and selective synthetic thrombin inhibitor N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide was studied after various routes of administration and varying doses. The concentration in the bile was determined using a biological method, the reliability of which was checked by HPLC-determinations. The compound was excreted in the bile in biologically active unchanged form. Cumulative biliary excretion of the synthetic thrombin inhibitor in rabbits amounted to a high percentage of the administered dose after low doses given either systemically or intraportally. In rats the excretion rates during and after intravenous infusion reached a maximum indicating saturation kinetics. Hepatic uptake and biliary excretion of the highly basic benzamidine derivative essentially contribute to its short plasma half-life.
Hauptmann
J
J
Institute of Pharmacology and Toxicology, Medical Academy Erfurt, GDR.
Kaiser
B
B
Paintz
M
M
Markwardt
F
F
D000578:Amidines / Q000493:pharmacokinetics*; D000818:Animals; D001550:Benzamidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism*; D001681:Biological Assay; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides; D005260:Female; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010880:Piperidines / Q000493:pharmacokinetics; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000578:Amidines; D001550:Benzamidines; D004151:Dipeptides; D010880:Piperidines; C038708:N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide; D013917:Thrombin