title: Gemfibrozil absorption and elimination in kidney and liver disease.
abstract: The disposition of the lipid-lowering drug gemfibrozil was studied in patients with either renal (n = 8) or hepatic disease (n = 8) and compared to those of healthy volunteers (n = 6). Gemfibrozil was determined in plasma and urine by means of a HPLC method. Urine was also analyzed for gemfibrozil conjugates. Following oral administration of 900 mg gemfibrozil, maximal plasma levels of the parent drug were 46.1 +/- 15.8 micrograms/ml, attained after 2.2 +/- 1.1 h. In chronic renal failure and in liver cirrhosis the plasma concentrations of gemfibrozil did not significantly differ from that of controls except in those patients who were co-medicated with antacids. These patients had significantly lower Cmax and AUC values. The elimination half-life of the drug was 1.5 h in controls, 2.4 h in renal failure, and 2.1 h in liver disease. In healthy volunteers, only 0.02 to 0.15% of the given dose was recovered in the urine as parent gemfibrozil, while conjugates made up 7-14%. In patients with renal failure also, only traces of parent gemfibrozil could be detected, and conjugates accounted for 0.5-9.8%. In those with liver disease, however, about 0.1-0.2% were recovered in urine as parent gemfibrozil and up to 50% as conjugates. Strikingly, the amount of excreted conjugates in the urine was positively correlated to the direct bilirubin plasma concentration.
authors.affiliation: Medizinische Klinik I, St. Bernward Krankenhaus, Hildesheim.
authors.forename: H
authors.initials: H
authors.lastname: Knauf
authors.forename: E U
authors.initials: EU
authors.lastname: Kölle
authors.forename: E
authors.initials: E
authors.lastname: Mutschler
mesh_terms: D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015248:Gemfibrozil / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D007674:Kidney Diseases / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D015248:Gemfibrozil