title: Pharmacokinetics and tissue penetration of a new carbapenem, doripenem, intravenously administered to laboratory animals.
abstract: The pharmacokinetic properties of doripenem following 20 mg/kg i.v. infusion were studied in various laboratory animals. The concentrations of doripenem in plasma, urine and tissue samples were determined by bioassay. Mean AUC0(0-infinityS) (microg x h/ml) and urinary recoveries (UR, %, 0-24 h) were 14.1 and 36.3 in mice, 9.3 and 42.1 in rats, 47.9 and 47.6 in rabbits, 78.6 and 83.1 in dogs and 44.1 and 51.0 in monkeys, respectively. In monkeys, with co-administration of probenecid, the mean AUC(0-infinity) of doripenem increased about 2.2 times and urinary excretion was delayed slightly. In mice, the doripenem level was highest in the blood plasma, followed by the kidney, liver, lung, heart and spleen. These doripenem levels in various tissues rapidly decreased and no accumulation was observed. Serum protein binding rates (%) of doripenem were 25.2 in mice, 35.2 in rats, 11.8 in rabbits, 10.2 in dogs, 6.1 in monkeys and 8.1 in humans, respectively.
authors.affiliation: Discovery Research Laboratories, Shionogi and Co., Ltd., Osaka 561-0825, Japan. toshihiko.hori@shionogi.co.jp
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hori
authors.forename: Masao
authors.initials: M
authors.lastname: Nakano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Murakami
mesh_terms: D000818:Animals; D019540:Area Under Curve; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004285:Dogs; D000077726:Doripenem; D005260:Female; D007262:Infusions, Intravenous; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D015780:Carbapenems; D000077726:Doripenem