Gemfibrozil absorption and elimination in kidney and liver disease.

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.