title: Ertapenem pharmacokinetics and pharmacodynamics during continuous ambulatory peritoneal dialysis.
abstract: Scant data exist for the pharmacokinetics (PK) of ertapenem in patients on continuous ambulatory peritoneal dialysis (CAPD). The goals of this study were to characterize the PK profile of ertapenem during CAPD, determine the extent of ertapenem penetration into the peritoneal cavity, and quantify the probability of the target attainment (PTA) profile in the serum and peritoneal cavity. A single-dose PK study was conducted in seven patients on CAPD. Population PK modeling and Monte Carlo simulation determined the probability that ertapenem at 500 mg intravenously (i.v.) every 24 h (q24h) would achieve concentrations in excess of the MIC for 40% of the dosing interval (40% T>MIC, where T is time) in the serum and peritoneal cavity. Monte Carlo simulation was also used to calculate the peritoneal cavity/serum mean and median penetration ratios by estimating the area under the concentration-time curve in the peritoneal cavity and serum (AUC(Peritoneal) and AUC(Serum), respectively) from zero to infinity after a single simulated dose. The population mean (± standard deviation [SD]) values for the apparent volume in the central compartment, clearance, and apparent volume in the peritoneal cavity were 2.78 (0.62) liters, 0.24 (0.07) liters/hr, and 5.81 (2.05) liters, respectively. The mean (SD) AUC(Peritoneal)/AUC(Serum) ratio was 1.039 (0.861), and the median penetration ratio was 0.801 (interquartile range, 0.486 to 1.317). In both the serum and peritoneal cavity, ertapenem at 500 mg i.v. q24h was very likely (>90%) to achieve the pharmacodynamic target for MICs of ≤2 mg/liter. The simulations suggest that 500 mg of ertapenem i.v. q24h is very likely to achieve the exposure target associated with clinical efficacy in both the serum and peritoneal cavity against the range of MIC values deemed susceptible by the Clinical and Laboratory Standards Institute.
authors.affiliation: Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Cardone
authors.forename: Darren W
authors.initials: DW
authors.lastname: Grabe
authors.forename: Robert W
authors.initials: RW
authors.lastname: Kulawy
authors.forename: Rachid
authors.initials: R
authors.lastname: Daoui
authors.forename: Joseph
authors.initials: J
authors.lastname: Roglieri
authors.forename: Shari
authors.initials: S
authors.lastname: Meola
authors.forename: George L
authors.initials: GL
authors.lastname: Drusano
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Lodise
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D000077727:Ertapenem; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D010529:Peritoneal Cavity / Q000502:physiology; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000379:methods*; D014556:Urine / Q000737:chemistry; D047090:beta-Lactams / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000077727:Ertapenem
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