Pharmacokinetics of meropenem in patients with liver disease.

Eight subjects with chronic stable alcoholic cirrhosis and eight matched controls with normal liver function were given an initial 30-minute intravenous infusion of 1 g of meropenem; beginning 24 hours later, they received five additional 1-g doses at 6-hour intervals. No statistically significant differences were found between the first dose and steady state or between groups for any plasma pharmacokinetic parameters-including the highest observed plasma concentrations, plasma concentrations at 6 hours after dosing (C6h), terminal half-life, area under the plasma concentration-time curve (AUC), area under the first moment of the curve, plasma clearance, steady-state volume of distribution, and accumulation ratios-on the basis of either AUC or C6h. There were also no statistically significant differences in any of the measured or calculated pharmacokinetic parameters of the microbiologically inactive metabolite of meropenem (ICI 213,689). A total of 11 adverse experiences (one moderate and 10 mild) were reported by four patients; nine of these experiences, including two in controls, were rated by the investigator as "possibly" drug related. It is concluded that meropenem is well tolerated with repeated intravenous dosing and that dosage adjustments are not necessary for patients with hepatic disease.