[Clinical pharmacokinetics of an imipenem-cilastatin combination]

Abstract

In the combination of imipenem (antibiotic of the thienamycin class, in the beta-lactam family) with cilastatin (renal dehydropeptidase I inhibitor) the ratio is 1:1. The urinary excretion of imipenem shows considerable interindividual variations due to the activity of renal dehydropeptidase I which degrades the compound. This makes it difficult to determine a mean dosage for therapeutic uses. However, when the dehydropeptidase I inhibitor cilastatin is given concomitantly with imipenem the urinary excretion and clearance of imipenem reach similar values in all subjects; in addition, the antibiotic is better tolerated by the kidney. Moreover, cilastatin has been shown to increase by 15 to 20 per cent the area under the imipenem plasma concentration curve. Following an intravenous infusion of imipenem 500 mg, the main pharmacokinetic values for the antibiotic are: area under the plasma concentration curve 43.2 +/- 4.7 h.mg/l; plasma clearance 195 +/- 25 ml/min; half-life 1.0 +/- 0.1 h; apparent volume of distribution 10.4 +/- 1.7 l. With repeated infusions of 500 ml every 6 to 8 hours, imipenem and cilastatin do not accumulate. In patients with renal impairment (creatinine clearance below 30 ml/min), cilastatin is excreted more slowly than imipenem and dosage must be adjusted accordingly.