PEFLOXACIN KINETICS IN CIRRHOSIS

Pefloxacin pharmacokinetics were evaluated in 16 patients with histologically proved cirrhosis of the liver and compared with those in 12 healthy subjects. In the patients with cirrhosis, the mean (.+-. SD) t1/2, although highly variable, was significantly longer (35.10 .+-. 19.00 hours) than in the normal subjects (11.00 .+-. 2.64 hours; P < 0.001). In the patients, the volume of distribution was decreased by 18% (P < 0.02) and total plasma clearance was markedly decreased (2.66 .+-. 1.85 vs. 8.19 .+-. 2.80 L/hr .cntdot. 1.73 m2; P < 0.001). The t1/2 was longer in patients with ascites or jaundice than in patients without these complications. The urinary excretion of unchanged pefloxacin was higher in the patients than in the subjects, while the excretion of N-desmethyl pefloxacin (a major metabolite of the drug) was lower. It is proposed that the decreased plasma clearance of pefloxacin in patients with cirrhosis is a result of decreased hepatic metabolism of the drug, and that the dosage should probably be modified in these patients.