Pharmacokinetics, Safety, and Tolerability of Doripenem After 0.5‐, 1‐, and 4‐Hour Infusions in Healthy Volunteers

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Abstract
The pharmacokinetics, safety, and tolerability of doripenem in healthy subjects were evaluated in 2 studies. Study 1 was a double‐blind, randomized, placebo‐controlled dose‐escalation study in which doripenem was administered for 7 days by infusion over 30 minutes (500 mg) or 1 hour (1000 mg). Study 2 was an open‐label, randomized, 3‐way crossover study in which each subject received a single dose of each of the following doripenem treatments on separate occasions: 500 mg infused over 1 hour, 500 mg infused over 4 hours, and 1000 mg infused over 4 hours. Doripenem exhibited linear pharmacokinetics with concordance between the studies for pharmacokinetic parameters. Doripenem did not accumulate with repeated dosing over 7 days. The area under the plasma concentration‐time curve (AUC) for doripenem 500 mg infused over 1 hour versus 4 hours was bioequivalent, and the AUC and Cmax increased proportionally with dose for the 500‐ and 1000‐mg doses administered over 4 hours. These results, along with the stability profile of doripenem, support its use as a prolonged infusion. All regimens of doripenem were safe and well tolerated.

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