Imipenem pharmacokinetics and body fluid concentrations in patients receiving high-dose treatment for serious infections.

Serum, urine, tissue, and body fluids were collected from 40 adult patients who were receiving imipenem/cilastatin treatment for serious infections. Thirty-two patients were given 1 g every 6 h (4 g/day), and eight received 500 mg (2 g/day). Mean peak concentrations in serum were 34.9 +/- 4.0 micrograms/ml for the 1-g dose and 26.6 +/- 2.5 micrograms/ml for the 500-mg dose. Trough levels were 3.1 and 1.0 micrograms/ml, respectively. No evidence of drug accumulation was found after comparing peaks measured early in the treatment with those measured late. Peak levels were only marginally increased when infusions were given over 30 versus 60 min. The mean serum half-life was 82.0 +/- 25.3 min, with a range of 50 to 138 min. The apparent volume of distribution was 0.35 +/- 0.13 liter/kg, and the mean total body clearance was 0.183 +/- 0.067 liter/kg per h. Creatinine clearance correlated directly with the plasma elimination rate and inversely with the serum half-life. Moreover, total body clearance fell as the age of the patient rose. The mean urinary recovery was 39.1 +/- 12.8% (range, 15.0 to 59.2%) and did not correlate with creatinine clearance until it was below 15 ml/min. Of 20 specimens of various gastrointestinal secretions, 13 had imipenem concentrations that were low, but above the MIC for most resident flora. Pus, sputum, and bone all had concentrations of the drug sufficient to inhibit the infecting organisms, and these levels reflected generally excellent clinical responses.