title: Pharmacokinetics of single-dose doripenem in adults with cystic fibrosis.
abstract: The pharmacokinetics of doripenem and doripenem-M-1 (inactive metabolite) were evaluated in an open-label, 2-period, single-sequence study in which single 1-g and 2-g doses of doripenem were administered intravenously over 4 hours to adult patients with cystic fibrosis (CF). The systemic exposure to doripenem and doripenem-M-1, as measured by observed apparent maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC), increased approximately proportionally to the increase in dose. Other pharmacokinetic parameters of doripenem and doripenem-M-1, including clearance, volume of distribution, and elimination half-life, were similar for the 1-g and 2-g doses. The results from this study were also compared with those from a previous study in adult healthy volunteers (HVs) without CF, from a previously conducted pharmacokinetic study, who received single doses of 500 mg and 1 g doripenem administered over 4 hours. The pharmacokinetics of doripenem in adult patients with CF are similar to those from adult HVs, noting some differences in the disposition when comparing body mass index-adjusted pharmacokinetic parameters.
authors.affiliation: Clinical Pharmacology Leader, J&J Pharmaceutical Research & Development, LLC, 920 Route 202 South, Raritan, NJ 08869-3509, USA. icirillo@its.jnj.com
authors.forename: Iolanda
authors.initials: I
authors.lastname: Cirillo
authors.forename: Nicole
authors.initials: N
authors.lastname: Vaccaro
authors.forename: Rebecca
authors.initials: R
authors.lastname: Redman
authors.forename: Philip L
authors.initials: PL
authors.lastname: Black
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kearns
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015780:Carbapenems / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003550:Cystic Fibrosis / Q000378:metabolism*; D000077726:Doripenem; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem