Pharmacokinetics of warfarin in the nephrotic syndrome and effect on vitamin K-dependent clotting factors

The behavior of warfarin, a drug tightly bound to albumin, was studied in patients with nephrotic syndrome (NS) to assess the influence of hypoalbuminemia on its pharmacokinetics and its effect on vitamin K-dependent coagulation factors. A single dose of warfarin (8 mg) was given orally to 11 nephro...

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Published inClinical nephrology Vol. 25; no. 2; p. 75
Main Authors Ganeval, D, Fischer, A M, Barre, J, Pertuiset, N, Dautzenberg, M D, Jungers, P, Houin, G
Format Journal Article
LanguageEnglish
Published Germany 01.02.1986
Subjects
Adolescent
Adult
Blood Coagulation Factors
Factor IX - metabolism
Factor VII - metabolism
Factor X - metabolism
Female
Humans
Kinetics
Male
Middle Aged
Nephrotic Syndrome - metabolism
Nephrotic Syndrome - physiopathology
Prothrombin - metabolism
Serum Albumin - metabolism
Vitamin K - metabolism
Warfarin - metabolism
Warfarin - pharmacology
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Summary:The behavior of warfarin, a drug tightly bound to albumin, was studied in patients with nephrotic syndrome (NS) to assess the influence of hypoalbuminemia on its pharmacokinetics and its effect on vitamin K-dependent coagulation factors. A single dose of warfarin (8 mg) was given orally to 11 nephrotic patients with normal or nearly normal renal function and to 11 controls. In every subject the following measurements were performed: albuminemia before (t0) warfarin administration; plasma warfarin and vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) levels, before and at time intervals from 0 to 48 h after drug administration; warfarin urinary excretion from 0 to 24 h. Urinary warfarin excretion was null in 19 out of the 22 subjects and very low in two nephrotic patients and in one control. Low serum albumin in NS patients induced a twofold increase of unbound warfarin vs controls (3.5% vs 1.8%, p less than 0.001) which led to a threefold increase in plasma clearance of warfarin (9.70 vs 3.26 ml X min-1, p less than 0.001); as warfarin distribution volume showed only a slight (non significant) increase in NS patients, the elimination half-life was thus markedly shortened in NS patients vs controls (18 vs 36 h, p less than 0.01). Maximum warfarin effect on vitamin K-dependent factor levels occurred at 18 h in controls and 24 h in nephrotics, and these lowest values were similar, in spite of a higher level at 0 in NS patients.
ISSN:0301-0430