PHARMACOKINETICS OF MEROPENEM IN PATIENTS WITH INTRAABDOMINAL INFECTIONS

Noncompartmental and compartmental analyses of meropenem disposition i n patients receiving 1-g intravenous intermittent infusions every 8 h were performed. Twelve patients (one woman and 11 men) participated in the meropenem pharmacokinetic analysis. Operative findings included p erforated appendicitis (five patients), gangrenous appendicitis (five patients), peri-appendical abscess (one patient), and gunshot wound to the abdomen (one patient). The most common associated adverse drug re actions to meropenem were diarrhea and increased liver enzymes. The es timated noncompartmental pharmacokinetic parameters, mean +/- standard deviation, are as follows: maximum drug concentration in plasma, 47.5 8 +/- 17.59 mug/ml; half-life, 1.04 +/- 0.19 h; elimination rate const ant, 0.68 +/- 0.12 h-1; area under the concentration-time curve from 0 h to infinity, 57.5 +/- 20.12 mug . ml/h; total plasma clearance, 315 .40 +/- 71.94 ml/min; renal clearance, 136.7 +/- 89.20 ml/min; volume of distribution at steady state, 26.68 +/- 6.88 liters; and mean resid ence time, 1.47 +/- 0.28 h. The two-compartment model best described m eropenem disposition in our patients. Our findings differed from estim ates for healthy volunteers possibly because of the physiologic change s as a result of surgery. Our findings suggest that meropenem (1,000 m g) administered intravenously every 8 h provides adequate concentratio ns for most intra-abdominal infections.