Pharmacokinetics of moxalactam in subjects with normal and impaired renal function

The pharmacokinetics of moxalactam were investigated in five subjects with normal renal function and 21 uremic patients. Normal subjects were given intravenous doses of 7.5 and 15 mg of the drug per kg as bolus injections (1 min) and 30 mg of the drug per kg as a 20-min infusion. Pharmacokinetic data, calculated by using a two-compartment open body model, were similar for the three intravenous doses: the t 1/2 alpha value was within 0.12 to 0.20 h, the t 1/2 beta value was 1.98 to 2.05 h, the central distribution volume (Vc) was 3.81 to 7.04 liters/1.73 m2, and the apparent volume of distribution at steady state (Vdss) was 9.12 to 13.36 liters/1.73 m2, i.e., 13.7 to 20.2% of the body weight. From 82.0 to 97.7% of the dose was recovered, in unchanged form, in urine during 24 h. After a single intramuscular dose of 15 mg/kg in the same subjects with normal renal function, the mean peak serum levels, occurring at 0.95 +/- 0.37 h, were 48.28 +/- 11.81 microgram/ml, the t 1/2 beta value was 2.22 +/- 0.16 h, the renal clearance (CR) was 87.5 +/- 9.4 ml/min per 1.73 m2, and 96.9 +/- 12.7% of the injected dose was found in 24-h urine. Pharmacokinetic data were similar for the two routes of administration. In uremic patients, the t 1/2 beta increased according to the severity of renal failure; it was 4.83 h in patients with creatinine clearances (Ccr) within 30 to 60 ml/min per 1.73 m2, 8.42 h for Ccr values within 10 to 30 ml/min, and 18.95 h in hemodialysis patients. During a 4- to 6-h dialysis session, the t 1/2 beta value was 3.65 h and 51% of the drug was removed by dialysis. The apparent volume of distribution at steady state increased in patients with Ccr values below 10 ml/min; serum and renal clearances decreased in uremic patients, and the nonrenal clearances remained constant in all these patients. From these pharmacokinetic results, linear relationships were found between the kinetic data and the biological parameters of the glomerular filtration rate. Dosage schedules were established, adapted to the degree of renal impairment.