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. 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 micrograms.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 liver-function 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Triger
D R
DR
Medical School, University of Sheffield, United Kingdom.
Granai
F
F
Woodcock
J
J
Wise
R
R
Imbimbo
B P
BP
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004334:Drug Administration Schedule; D005260:Female; D024841:Fluoroquinolones; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C060328:rufloxacin