ABSTRACT
Multiple doses of imipenem/cilastatin were administered to patients with end-stage renal disease undergoing long-term hemodialysis. Schedules of 250 mg every six hours, 500 mg every six hours, and 500 mg every 12 hours were studied. Five hundred mg every 12 hours was the most efficient schedule that maintained effective trough antibiotic activity. Twelve volunteers including two patients with clinical infections using the dose schedule of 500 mg every 12 hours received imipenem/cilastatin for two to 14 days without any notable clinical side effects. Imipenem peak and trough concentrations averaged 29 +/- 5 micrograms/ml and 10 +/- 3 micrograms/ml, respectively. No accumulation of imipenem occurred during the trial. Cilastatin peak and trough concentrations were 89 +/- 38 micrograms/ml and 70 +/- 27 micrograms/ml, respectively. The plasma concentration of cilastatin increased with each dose until the next hemodialysis session.
Subject(s)
Cyclopropanes/metabolism , Kidney Failure, Chronic/metabolism , Renal Dialysis , Thienamycins/metabolism , Aged , Cilastatin , Cyclopropanes/administration & dosage , Drug Combinations , Humans , Imipenem , Middle Aged , Thienamycins/administration & dosageABSTRACT
The pharmacokinetics of ceforanide were evaluated in 11 patients with end stage renal disease (creatinine clearance less than 5 ml/min). A single intravenous dose of 750 mg/m2 produced peak plasma concentrations of 123 +/- 29 microgram/ml. The plasma half-life (T 1/2) of the drug was 19.1 +/- 2.5 h. A 5.5 h hemodialysis session removed 53% of the drug and reduced the T 1/2 to 5 +/- 0.7 h. Plasma concentrations greater than 10 microgram/m2 were maintained without adverse effects with a 1.5-g/m2 dose administered three times a week for 2 weeks.
