Population pharmacokinetics and dosing simulations of imipenem in serious bacteraemia in immunocompromised patients with febrile neutropenia.
The aims of this study were to i) reveal the population pharmacokinetics; and ii) assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) (defined as the expected population PTA for a specific drug dose and a specific population of microorganisms) of imipenem in febrile neutropenic patients with bacteraemia. Ten patients were randomised into two groups: Group I received a 0.5-h infusion of 0.5 g of imipenem every 6 h (q6h) for 8 doses; and Group II received a 4-h infusion of 0.5 g q6h for 8 doses. A Monte Carlo simulation was performed to determine the PTA. The volume of distribution and total clearance of imipenem were 20.78 ± 1.35 l and 23.19 ± 1.34 l/h, respectively. Only a 4-h infusion of 1 g q6h regimen achieved a PTA >93% for 80% T>MIC for a MIC of 2 μg/ml. A 4-h infusion of all simulated regimens and a 0.5-h infusion of 0.5 g q6h and 1 g q6h achieved targets (CFR ≥ 90%) against Escherichia coli and Klebsiella spp. However, against Pseudomonas aeruginosa and Acinetobacter spp., no regimens achieved their targets. In conclusion, the results indicate that a higher than manufacturer's dosage recommendation is required to maximize the activity of imipenem.
Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand. Electronic address: jasutep@medicine.psu.ac.th.
Sutep
S
Jaruratanasirikul
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand.
Wibul
W
Wongpoowarak
Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand.
Monchana
M
Jullangkoon
Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand.
Maseetoh
M
Samaeng
D000150:Acinetobacter / Q000187:drug effects; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D016470:Bacteremia / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects; D064147:Febrile Neutropenia / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D016867:Immunocompromised Host; D007262:Infusions, Intravenous; D007709:Klebsiella / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012720:Severity of Illness Index; D055815:Young Adult
D000900:Anti-Bacterial Agents; D015378:Imipenem
Febrile Neutropenia; Imipenem; Pharmacodynamics; Pharmacokinetics/pharmacodynamics; Population pharmacokinetics