Pharmacokinetics of Single-Dose Doripenem in Adults With Cystic Fibrosis

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 (Cmax) 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.