title: Clinical pharmacokinetics of meropenem in pancreatic juice and site-specific pharmacodynamic target attainment against Gram-negative bacteria: dosing considerations.
abstract: OBJECTIVE
  Very few studies have revealed the dynamics of meropenem penetration into the pancreas or pancreatic juice in humans. This study of the clinical pharmacokinetics and pharmacodynamics of meropenem in human pancreatic juice was performed to establish a basis for the validation of dosing regimens for pancreatic infections.
  
  
  METHODS
  Ten patients with endoscopic naso-pancreatic drainage received 500 mg meropenem over 0.5 h via intravenous infusion. Venous blood and pancreatic juice samples were collected post-infusion for up to 5.0 h and used to obtain measures of meropenem concentration. The probability of attaining the pharmacodynamic target (40% of the time above the minimum inhibitory concentration [MIC]) in pancreatic juice against MIC distributions for clinical isolates of Gram-negative bacteria was determined using a Monte Carlo simulation.
  
  
  RESULTS
  The mean maximum concentration of meropenem in pancreatic juice was 2.08 ± 0.94 μg/mL at 1.025 ± 0.18 h. The pancreatic juice/plasma ratio was 0.055 ± 0.028. A 0.5-h infusion of 500 mg meropenem every 8 h achieved a 99.4% probability of target attainment against Escherichia coli, 96.4% against Klebsiella species, 94.3% against Enterobacter species and 96.2% against Proteus species, but only 41.3% against Pseudomonas aeruginosa isolates.
  
  
  CONCLUSIONS
  Intravenous meropenem exhibits low penetrance into pancreatic juice. However, a dosing regimen of 500 mg meropenem (0.5-h infusion) every 8 h provides sufficient drug-exposure time in pancreatic juice against the four common Gram-negative bacteria populations.
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Japan. Electronic address: k-naru-surg@hiroshima-u.ac.jp.
authors.forename: Naru
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Clinical Pharmacotherapy, Institute of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Uemura
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sudo
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohge
authors.affiliation: Department of Clinical Pharmacotherapy, Institute of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.affiliation: Department of Surgery, Institute of Biomedical and Health Sciences, Hiroshima University, Japan.
authors.forename: Taijiro
authors.initials: T
authors.lastname: Sueda
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004322:Drainage; D004724:Endoscopy; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010189:Pancreatic Juice / Q000378:metabolism*; D011446:Prospective Studies; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem
keywords: Dosing regimen; Meropenem; Pancreatic juice; Pharmacokinetics