MULTIPLE-DOSE PHARMACOKINETICS OF RUFLOXACIN IN PATIENTS WITH CIRRHOSIS

The multiple-dose pharmacokinetics of rufloxacin were investigated in 13 patients with biopsy-proven cirrhosis and in 5 healthy controls. Ru floxacin 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 da ys. Plasma and urinary drug concentrations were determined by high-per formance liquid chromatography and a microbiological assay. A one-comp artment model applied to the high-performance liquid chromatography da ta was used to calculate the pharmacokinetic parameters of rufloxacin. In the controls rufloxacin had a low plasma clearance (41 +/- 4 ml/mi n, 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 mug . hr/ml) and a low renal clearance (18 +/- 2 ml/min). No appreciable differenc es were observed in the pharmacokinetic parameters between patients wi th various degrees of liver-function impairment (modified Child-Pugh s core ranging from 5 to 13). In these patients plasma clearance was sli ghtly reduced (-32%), but this decrease was caused by a marked reducti on in renal clearance (-65%) rather than nonrenal clearance, which rem ained unchanged (22 ml/min in cirrhotic patients vs. 23 ml/min in cont rols). A significant (p < 0.01) correlation was found between creatini ne clearance and both rufloxacin renal clearance (r = 0.769) and ruflo xacin plasma clearance (r = 0.681). The elimination half-life and the area under the plasma concentration vs. time curve were moderately inc reased in cirrhotic patients ( + 33% and + 26%, respectively). These f indings indicate that factors related to declining renal function, rat her than liver impairment itself, may be the prime cause in determinin g alterations in the pharmacokinetic parameters in cirrhotic patients. When these patients have normal renal function. no dose adjustment is needed during oral rufloxacin treatment.