PMID: 3701606Mar 1, 1986

Apparent dose dependency of the hepatic (S)-acenocoumarol clearance in the rat: a study using open liver biopsies

Journal of Pharmaceutical Sciences
M J DaemenH H Thijssen


Saturable hepatic uptake processes may account for the apparent dose-dependent clearance of 4-hydroxycoumarins. We investigated the dose dependent clearance and dose dependent liver distribution of the (S)-enantiomer of acenocoumarol (4-hydroxy-3-[1-4-nitrophenyl)-3-oxobutyl]coumarin) in the rat applying the in situ liver biopsy technique. The drug was administered by constant-rate infusion. At infusion rates below 0.6 microgram/min, blood clearance appeared to be dose dependent, i.e., clearance of (S)-acenocoumarol declined gradually from 6.5 mL/min at a 0.15 microgram/min infusion rate to 3.9 mL/min at a 0.6 micrograms/min infusion rate. From 0.6 microgram/min up to the highest input tested, i.e., 15 micrograms/min, clearance was almost constant, 3.5 mL/min. At low infusion rates the steady-state liver concentration of (S)-acenocoumarol rose steeply in a convex way with infusion. Scatchard analysis of steady-state liver concentrations in relation to steady-state blood concentrations revealed a hepatic binding site for (S)-acenocoumarol, exhibiting a capacity of 1.4 microgram/g of liver tissue.


Feb 1, 1980·AJR. American Journal of Roentgenology·J ZornozaJ Lukeman


Nov 6, 1991·Biochemical Pharmacology·H H Thijssen, L G Baars
Aug 1, 1997·Pathology·P L CmielewskiP M Hall
Apr 1, 1989·Biochemical Pharmacology·H H Thijssen, L G Baars
Dec 18, 2001·Journal of Applied Physiology·Victoria Matas BonjornJean-Marc Lavoie

Related Concepts

Dose-Response Relationship, Drug
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