title: An Open, Randomized, Single-Center, Crossover Pharmacokinetic Study of Meropenem after Intraperitoneal and Intravenous Administration in Patients Receiving Automated Peritoneal Dialysis.
abstract: The objective of this study was to determine the pharmacokinetic profile of meropenem in automated peritoneal dialysis (APD) patients. In 6 patients without peritonitis, a single dose of 0.5 g of meropenem was applied intraperitoneally (i.p.) or intravenously (i.v.) and concentrations in serum and dialysate were measured at specified intervals over 24 h with high-performance liquid chromatography-mass spectrometry. The mean maximum concentrations of meropenem in serum (Cmax) were 27.2 mg/liter (standard deviation [SD], ±6.9) and 10.1 mg/liter (SD, ±2.5) and in dialysate were 3.6 mg/liter (SD, ±2.3) and 185.8 mg/liter (SD, ±18.7) after i.v. and i.p. administrations, respectively. The mean areas under the curve from 0 to 24 (AUC0-24) of meropenem in serum were 173.5 mg · h/liter (SD, ±29.7) and 141.4 mg · h/liter (SD, ±37.5) (P = 0.046) and in dialysate were 42.6 mg · h/liter (SD, ±20.0) and 623.4 mg · h/liter (SD, ±84.1) (P = 0.028) after i.v. and i.p. administrations, respectively. The ratios for dialysate exposure over plasma exposure after i.v. and i.p. treatments were 0.2 (SD, ±0.1) and 4.6 (SD, ±0.9), respectively (P = 0.031). A mean target value of 40% T>MIC (time for which the free meropenem concentration exceeds the MIC) for clinically relevant pathogens with EUCAST susceptibility breakpoints of 2 mg/liter was reached in serum after i.p. and i.v. administrations and in dialysate after i.p. but not after i.v. administration. The present data indicate that low i.p. exposure limits the i.v. use of meropenem for PD-associated peritonitis. In contrast, i.p. administration not only results in superior concentrations in dialysate but also might be used to treat systemic infections.
authors.affiliation: Department of Internal Medicine I, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria.
authors.forename: Martin
authors.identifier: 0000-0003-3618-6268
authors.initials: M
authors.lastname: Wiesholzer
authors.affiliation: Department of Internal Medicine I, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria.
authors.forename: Petra
authors.initials: P
authors.lastname: Pichler
authors.affiliation: Department of Pharmacognosy, University of Vienna, Vienna, Austria.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Reznicek
authors.affiliation: Department of Internal Medicine I, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria.
authors.forename: Michaela
authors.initials: M
authors.lastname: Wimmer
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Manuel
authors.initials: M
authors.lastname: Kussmann
authors.affiliation: Department of Internal Medicine I, University Hospital St. Poelten, Karl Landsteiner University of Health Sciences, St. Poelten, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Balcke
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Burgmann
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria markus.zeitlinger@meduniwien.ac.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.affiliation: Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poeppl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D013058:Mass Spectrometry; D000077731:Meropenem; D008875:Middle Aged; D010530:Peritoneal Dialysis; D013845:Thienamycins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem