Pharmacokinetics of parenteral imipenem/cilastatin in patients on continuous ambulatory peritoneal dialysis.
We investigated the pharmacokinetics of two intravenous (iv) dose regimens of imipenem/cilastatin in Chinese patients on chronic ambulatory peritoneal dialysis (CAPD), who had an average creatinine clearance of 3.2 ml/min/1.73 m2. Doses of 0.5 and 1.0 g produced mean peak serum imipenem concentrations of 30 and 70 mg/l respectively, about 60% of cilastatin. Peritoneal dialysis fluid (PDF) imipenem concentrations reached 20-30% of the serum peak 4-5 h after iv injection, and the lowest maximum PDF concentrations were 2 mg/l after the 0.5 g dose and 14 mg/l after 1.0 g. Thus both regimes produced PDF imipenem concentrations above the MICs of susceptible pathogens. The half-life of imipenem was 6.4 h and the plasma clearance 66 ml/min; serum and PDF imipenem were in equilibration after about 5 h. Cilastatin had a prolonged half-life of 19 h and a plasma clearance of 10 ml/min, and accumulated in both serum and PDF. With a 0.5 g dose, the pharmacokinetics of imipenem/cilastatin suggest that the combination may prove an effective treatment for peritonitis associated with CAPD.
Chan
C Y
CY
Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories.
Lai
K N
KN
Lam
A W
AW
Li
P K
PK
Chung
W W
WW
French
G L
GL
D000328:Adult; D015377:Cilastatin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077728:Cilastatin, Imipenem Drug Combination; D003404:Creatinine / Q000378:metabolism; D015314:Dialysis Solutions / Q000032:analysis*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D013997:Time Factors
D015314:Dialysis Solutions; D004338:Drug Combinations; D015377:Cilastatin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D003404:Creatinine