This study was supported by an investigator-initiated research grant from Merck & Co., Inc.
Original Research Article
Comparative Pharmacokinetics, Pharmacodynamics, and Tolerability of Ertapenem 1 Gram/Day Administered as a Rapid 5-Minute Infusion versus the Standard 30-Minute Infusion in Healthy Adult Volunteers
Article first published online: 11 FEB 2013
© 2013 Pharmacotherapy Publications, Inc.
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Volume 33, Issue 3, pages 266–274, March 2013
How to Cite
Presented in part at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, Illinois, September 17–20, 2011.
ClinicalTrials.gov identifier: NCT01148771 (http://www.clinicaltrials.gov/ct2/show/NCT01148771).
- Issue published online: 1 MAR 2013
- Article first published online: 11 FEB 2013
- Merck & Co., Inc
- intravenous bolus;
To compare ertapenem pharmacokinetics, pharmacodynamics, and tolerability when administered as a rapid 5-minute infusion to the standard 30-minute infusion.
Prospective, randomized, crossover pharmacokinetic study.
Clinical research center.
Twelve healthy adult volunteers.
Each subject received ertapenem 1 g intravenously, administered either as a rapid 5-minute infusion or the standard 30-minute infusion, every 24 hours for 3 days (first phase); after a 4-day washout period, each subject then received the other infusion every 24 hours for 3 days (second phase).
Measurements and Main Results
Plasma samples were collected after the first and third (steady-state) doses of each study phase, and protein binding was assessed by use of ultrafiltration. Pharmacokinetic analyses were conducted using noncompartmental and compartmental methods. A 5000-subject Monte Carlo simulation was used to assess the probability of target attainment for free drug concentration remaining above the minimum inhibitory concentration (MIC) for 40% or greater of the dosing interval (40% fT > MIC) over an MIC range. Ertapenem was well tolerated and adverse events were similar for both infusions. The ertapenem steady-state mean ± SD maximum concentrations were 193.3 ± 43.3 and 165.7 ± 20.4 mg/L for the 5- and 30-minute infusions, respectively; the mean ± SD areas under the concentration-time curves from 0–24 hours were 561.2 ± 77.0 and 531.3 ± 56.9 μg · hr/ml (geometric mean ratio 1.008, 90% confidence interval 0.999–1.017), respectively. Protein binding was concentration dependent (range 87.9–98.9%). A two-compartment model best described ertapenem pharmacokinetics with the following parameter estimates: clearance 1.89 ± 0.19 L/hr, volume of central compartment 5.04 ± 0.56 L, and transfer constants k12 0.43 ± 0.08/hr and k21 0.44 ± 0.07/hr. The probabilities of target attainment for 5- and 30-minute infusions were 97.0% and 97.9% at an MIC of 0.25 mg/L and 1.7% and 2.8% at an MIC of 0.5 mg/L, respectively.
Ertapenem administered as a rapid 5-minute infusion provides a well tolerated, bioequivalent, and pharmacodynamically equivalent regimen to the 30-minute infusion at clinically relevant MICs.