title: Doripenem pharmacokinetics in critically ill patients receiving continuous hemodiafiltration (CHDF).
abstract: Objectives of the prospective, open-label study were to investigate pharmacokinetics of doripenem and determine appropriate doripenem regimens during continuous hemodiafiltration (CHDF) in critically ill patients with renal failure (creatinine clearance <30 ml/min) in the intensive care unit at a university hospital in Japan. Six patients received intravenous (IV) administration of 250 mg of doripenem every 12 or 24 hours during CHDF (dialysis rate, 500 ml/h; hemofiltration rate, 300 ml/h) via a polysulfone hemofilter. Doripenem concentrations in pre- and post-membrane blood (plasma) samples collected at specified times during one dosing interval were measured in order to calculate pharmacokinetic parameters and clearance via hemodiafiltration. Mean half-life (+/-standard deviation) of doripenem was 7.9+/-3.7 hours. Total body clearance of doripenem was 58.0+/-12.7 ml/min, including clearance of 13.5+/-1.6 ml/min via CHDF. An IV dose of 250 mg of doripenem every 12 hours during CHDF provided adequate plasma concentrations for critically ill patients with renal failure, without resulting in accumulation upon steady-state. Thus, under the conditions tested, CHDF appeared to have little effect on doripenem clearance. Therefore, the blood level of doripenem can be satisfactorily controlled by adjustment of doripenem dose and dosing interval, in accordance with residual renal function in patients receiving CHDF.
authors.affiliation: Department of Anesthesiology and Intensive Care, Faculty of Medicine, Oita University, Yufu, Oita, Japan. sehidaka@med.oita-u.ac.jp
authors.forename: Seigo
authors.initials: S
authors.lastname: Hidaka
authors.forename: Koji
authors.initials: K
authors.lastname: Goto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015780:Carbapenems / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016638:Critical Illness; D000077726:Doripenem; D005260:Female; D006207:Half-Life; D017583:Hemodiafiltration; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000378:metabolism* / Q000628:therapy*
chemical_list: D015780:Carbapenems; D000077726:Doripenem