Pharmacokinetics, safety, and tolerability of doripenem after 0.5-, 1-, and 4-hour infusions in healthy volunteers.
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.
Cirillo
Iolanda
I
J&J Pharmaceutical Research & Development LLC, Route 202, Raritan, NJ 08869-3509, USA.
Vaccaro
Nicole
N
Turner
Kenneth
K
Solanki
Bhavna
B
Natarajan
Jaya
J
Redman
Rebecca
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D015780:Carbapenems / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D000077726:Doripenem; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem