Steady-state pharmacokinetics of intramuscular imipenem-cilastatin in elderly patients with various degrees of renal function

We studied the concentrations in plasma and pharmacokinetics of imipenem and cilastatin in elderly patients (greater than 65 years old) who had various degrees of renal function and who were hospitalized with soft tissue infections. Three groups of patients received imipenem-cilastatin (500/500 mg) intramuscularly every 12 h: group I consisted of eight patients with a creatinine clearance (CLCR) of greater than 50 ml/min (range, 51 to 84 ml/min; mean, 65.8 ml/min); group II consisted of three patients with a CLCR of 20 to 50 ml/min; and group III consisted of two patients with a CLCR of less than 20 ml/min. Imipenem and cilastatin concentrations were measured at steady state on day 5. Mean peak and trough plasma imipenem concentrations were 5.28 +/- 1.78 and 1.43 +/- 0.76 micrograms/ml in group I, 6.25 +/- 0.78 and 2.50 +/- 0.00 micrograms/ml in group II, and 14.3 +/- 0.71 and 6.85 +/- 1.06 micrograms/ml in group III, respectively. Mean peak and trough plasma cilastatin concentrations were 11.8 +/- 2.85 and 0.31 +/- 0.43 microgram/ml in group I, 15.5 +/- 2.48 and 2.03 +/- 2.05 micrograms/ml in group II, and 24.5 +/- 6.72 and 10.7 +/- 5.94 micrograms/ml in group III, respectively. Mean imipenem AUCss (area under the concentration-time curve over a dosage interval at steady state) values were 38.7 +/- 7.9 micrograms.h/ml for group I, 52.3 +/- 7.3 micrograms.h/ml for group II, and 143.7 +/- 11.9 micrograms.h/ml for group III. Mean cilastatin AUCss values were 45.6 +/- 12.5 micrograms.h/ml for group I, 93.8 +/- 51.2 micrograms.h/ml for group II, and 217.5 +/- 57.8 micrograms.h/ml for group III. Cilastatin mean apparent body clearance values (normalized to weight) were 2.78 +/- 0.67 ml/min for group I, 1.43 +/- 0.81 ml/min for group II, and 0.71 +/- 0.24 ml/min for group III. Imipenem open-lactam metabolite levels were all below the level of detective of the assay (<3.9 micrograms/ml). There was a progressive increase in plasma imipenem and cilastatin levels and AUCss and there was a decline in body clearance as renal function declined.