The multiple-dose pharmacokinetics of rufloxacin were investigated in 13 patients with biopsy-proven cirrhosis and in 5 healthy controls. Rufloxacin was administered once a day for 5 consecutive days, starting with a loading dose of 400 mg on day 1 and 200 mg on the subsequent days. Plasma and urinary drug concentrations were determined by high-performance liquid chromatography and a microbiological assay. A one-compartment model applied to the high-performance liquid chromatography data was used to calculate the pharmacokinetic parameters of rufloxacin. In the controls rufloxacin had a low plasma clearance (41 ± 4 ml/min, mean ± S.E.M.), a long half-life (30.1 ± 3.9 hr), a large area under the plasma concentration vs. time curve (171 ± 18 μg · hr/ml) and a low renal clearance (18 ± 2 ml/min). No appreciable differences were observed in the pharmacokinetic parameters between patients with various degrees of liverfunction impairment (modified Child-Pugh score ranging from 5 to 13). In these patients plasma clearance was slightly reduced (−32%), but this decrease was caused by a marked reduction in renal clearance (−65%) rather than nonrenal clearance, which remained unchanged (22 ml/min in cirrhotic patients vs. 23 ml/min in controls). A significant (p < 0.01) correlation was found between creatinine clearance and both rufloxacin renal clearance (r = 0.769) and rufloxacin plasma clearance (r = 0.681). The elimination half-life and the area under the plasma concentration vs. time curve were moderately increased in cirrhotic patients (+33% and +26%, respectively). These findings indicate that factors related to declining renal function, rather than liver impairment itself, may be the prime cause in determining alterations in the pharmacokinetic parameters in cirrhotic patients. When these patients have normal renal function, no dose adjustment is needed during oral rufloxacin treatment. (HEPATOLOGY 1993;18:847-852).