PHARMACOKINETICS OF MEROPENEM IN PATIENTS WITH LIVER-DISEASE

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