Pharmacokinetics and pharmacodynamics of biapenem in critically ill patients under continuous venovenous hemodiafiltration.
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.
Suyama
Hidemichi
H
Critical Care Medical Center, Hiroshima Prefectural Hospital.
Ikawa
Kazuro
K
Morikawa
Norifumi
N
Ikeda
Kayo
K
Fujiue
Yoshihiro
Y
Morikawa
Shingo
S
Kaneko
Kotaro
K
Kuwabara
Masao
M
Yamanoue
Takao
T
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
D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D013845:Thienamycins; D014157:Transcription Factors; C073099:pros protein, Drosophila; C065257:biapenem