Serum levels of free non-protein bound clofibrinic acid after single dosing to patients with impaired renal function of various degrees--a multicenter study.
As a basis for establishing dosing guidelines in order to avoid side effects due to overdosage, the concentrations of total and free non-protein bound clofibrinic acid (CA) were determined before and after the administration of a single clofibrate dose (0, 2, 6, 12, 24, 48, 72, 96h) in patients with various degrees of impaired renal function and in a control group (n = 56). The clofibrate doses administered to the five groups were: group 0 = control group without renal impairment: 1,000 mg; group 1 = serum creatinine up to 354 mumol/l: 1,000 mg; group 2a = creatinine levels greater than 354 mumol/l up to levels requiring dialysis: 1,000 mg; group 2b = creatinine levels like 2a, but only 500 mg; group 3 = patients requiring dialysis: 500 mg. In addition, serum albumin, CK, GOT and GPT were controlled. Total CA was determined by gas chromatography, the unbound fraction by equilibrium dialysis. Increasing serum creatinine levels were correlated with a decrease of total CA but with a statistically significant increase in free CA concentrations. The levels of non-protein bound CA of groups 1 and 2a were significantly different from control group 0 (same dosing). In addition, a significantly negative correlation between free CA and serum albumin levels was demonstrated. Determination of free CA as a control parameter of clofibrate therapy in patients with impaired renal function allows clofibrate dosing to be closer related to the individual subject than the determination of total CA only.
D000328:Adult; D002994:Clofibrate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000008:administration & dosage / Q000097:blood*; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis
D012709:Serum Albumin; D002995:Clofibric Acid; D003404:Creatinine; D002994:Clofibrate