@article{2a99539acd1643c8b217ebbc9dc6c58b,
title = "Population Pharmacokinetic Modeling and Simulations of Imipenem in Burn Patients With and Without Continuous Venovenous Hemofiltration in the Military Health System",
abstract = "Continuous venovenous hemofiltration (CVVH) is a life-sustaining procedure in patients with severe burns and acute kidney injury. Physiologic changes from burn injury and use of CVVH may alter imipenem pharmacokinetics (PK). We aimed to compare imipenem clearance (CL) in burn patients with and without CVVH, determine the effect of burn on imipenem volume of distribution (CVVH, n = 12; no CVVH, n = 11), in combination with previously published models. Model qualification was performed with standard diagnostics and comparing predicted PK parameters/time-concentration profiles with those in the existing literature. Monte Carlo simulations were conducted to evaluate the probability of target attainment. A 2-compartment model best described the data. Utilizing albumin as a covariate on volume parameters and leveraging the clearance model from prior literature, our model predicted imipenem central volume and CL within a 10% margin of error across healthy, renally impaired, and burn populations. We provide direct comparison of imipenem CL in burn patients with and without CVVH. Notably, there was no significant difference. Large imipenem Vd in patients with severe burns is likely explained by increased capillary permeability, for which serum albumin may be a reasonable surrogate. Dosing 500 mg every 6 hours is adequate for burn patients on renally dosed CVVH; however, suspicion of augmented renal clearance or patients placed on CVVH without renal impairment may necessitate dosing of 1000 mg every 6 hours.",
keywords = "Monte Carlo simulations, antibiotic, burn, pharmacokinetics",
author = "Por, {Elaine D.} and Akers, {Kevin S.} and Chung, {Kevin K.} and Livezey, {Jeffrey R.} and Selig, {Daniel J.}",
note = "Funding Information: Funding provided by a Uniformed Services University of the Health Sciences (USUHS)/Walter Reed Army Institute of Research (WRAIR) Clinical Pharmacology (P8) Fellowship. Material has been reviewed by the Walter Reed Army Institute of Research, the Uniformed Services University of the Health Sciences, and the United States Institute of Surgical Research. There is no objection to its presentation and/or publication. The views expressed in this article are those of the authors and do not reflect the official policy or position of the U.S. Army Medical Department, Department of the Army, Department of Defense, or the U.S. government. This study was conducted under a protocol reviewed and approved by the U.S. Army Medical Research and Development Command Institutional Review Board and in accordance with the approved protocol. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70-25. We thank Ms. Zanete Wright for her support of the WRAIR/USUHS Clinical Pharmacology Fellowship. We also thank Dr. Vijay Gorantla and Dr. Joga Gobburu for their expertise and feedback on this study. This research would not have been possible without their assistance. Funding Information: Funding provided by a Uniformed Services University of the Health Sciences (USUHS)/Walter Reed Army Institute of Research (WRAIR) Clinical Pharmacology (P8) Fellowship. Publisher Copyright: {\textcopyright} Published 2021. This article is a U.S. Government work and is in the public domain in the USA. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology",
year = "2021",
month = sep,
doi = "10.1002/jcph.1865",
language = "English",
volume = "61",
pages = "1182--1194",
journal = "Journal of Clinical Pharmacology",
issn = "0091-2700",
number = "9",
}