Table of Contents
ISRN Pharmacology
Volume 2012, Article ID 782656, 10 pages
http://dx.doi.org/10.5402/2012/782656
Research Article

Doripenem Dosing Recommendations for Critically Ill Patients Receiving Continuous Renal Replacement Therapy

1Clinical Pharmacology, Janssen Research & Development, L.L.C., 920 Route 202, Raritan, NJ 08869, USA
2Clinical Research and Public Policy, School of Pharmacy, Virginia Commonwealth University, MCV Campus, 215 McGuire Hall, 1112 East Clay Street, P.O. Box 980533, Richmond, VA 23298, USA
3Clinical Development, Janssen Research & Development, L.L.C, 6500 Paseo Padre Parkway, B-1, Fremont, CA 94555, USA
4Clinical Pharmacology, Janssen Research & Development, L.L.C., 1125 Trenton-Harbourton Road, Titusville, NJ 08650, USA

Received 17 April 2012; Accepted 30 May 2012

Academic Editors: M. Brunner, K. Cimanga, and H. Kankaanranta

Copyright © 2012 Mahesh N. Samtani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Doripenem dosing regimens for patients receiving continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration (CVVHDF) were devised based on an established efficacy criterion (free plasma doripenem concentrations above the minimum inhibitory concentration [ 𝑓 T > M I C ] of 1 mg/L for ≥35% of the dosing interval) while maintaining exposure below that with the highest studied dose of 1000 mg infused over 1 hour every 8 hours in healthy subjects. Simulations were utilized to assure ≥90% probability of achieving the efficacy criterion with the recommended doripenem regimens. Inflated intersubject variability of 40% (coefficient of variation) was used for pharmacokinetic parameters (representative of clinical variation) and nonrenal clearance was doubled to account for potential changes with acute renal insufficiency. Results indicate that a reduction in doripenem dose will be needed for critically ill patients receiving CVVH or CVVHDF. This work was conducted to fulfill a health authority request and resulted in the addition of dosing recommendations to the Doribax Summary of Product Characteristics.