title: Pharmacokinetics and pharmacodynamics of biapenem in critically ill patients under continuous venovenous hemodiafiltration.
abstract: To characterize the PK/PD of biapenem (BIPM) in critically ill patients under continuous venovenous hemodiafiltration (CVVHDF), we conducted a prospective, open-label study in nine adult CVVHDF patients with acute renal failure at the Critical Care Medical Center, Hiroshima Prefectural Hospital. Plasma and filtrate samples were obtained at six time points. The concentrations of BIPM in plasma and filtrate were determined by HPLC. PK parameters were analyzed using Monte Carlo simulation with MIC data. BIPM concentrations in the plasma and CVVHDF filtrate peaked at the end of infusion, and the values were similar. The drug clearance by CVVHDF and non-CVVHDF was 1.28 +/- 0.14 and 9.05 +/- 4.05 L/h, respectively. Monte Carlo simulation showed that the more administration times, there were the higher the probability. In conclusion, a dosing regimen of 300 mg BIPM q8h had a higher probability of therapeutic efficacy than q12h in patients with severe sepsis under CVVHDF.
authors.affiliation: Critical Care Medical Center, Hiroshima Prefectural Hospital.
authors.forename: Hidemichi
authors.initials: H
authors.lastname: Suyama
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujiue
authors.forename: Shingo
authors.initials: S
authors.lastname: Morikawa
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kaneko
authors.forename: Masao
authors.initials: M
authors.lastname: Kuwabara
authors.forename: Takao
authors.initials: T
authors.lastname: Yamanoue
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy; D000328:Adult; D000368:Aged; D016638:Critical Illness; D029721:Drosophila Proteins; D024881:Drug Resistance, Bacterial; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013810:Therapeutic Equivalency; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors
chemical_list: D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D013845:Thienamycins; D014157:Transcription Factors; C073099:pros protein, Drosophila; C065257:biapenem