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)

A study of the penetration of meropenem into bile using endoscopic retrograde cholangiography.

One gram of meropenem was administered as prophylaxis to patients undergoing endoscopic retrograde cholangiography (ERC) in a study of the bile pharmacokinetics of this agent. Twenty-four patients were evaluated and a single bile sample was collected from each one during ERC at different time intervals following intravenous infusion. Bile concentrations after the dose ranged from 0.7 to 25.7 mg/L (mean 11.1) and exceeded the MIC90s for the pathogens most commonly associated with biliary tract infections for up to 203 mins. The bile concentrations of 13 patients with biliary tree obstruction were compared with those of 11 patients without obstruction. Bile concentrations in excess of the MIC90s for the predominant pathogens were achieved in both groups; a positive correlation between meropenem bile concentration and the time of dose administration was demonstrable only for the obstructed group. ERC may be a useful technique for biliary pharmacokinetic studies.