Population Pharmacokinetic Modeling and Simulations of Imipenem in Burn Patients With and Without Continuous Venovenous Hemofiltration in the Military Health System
Autor: | Jeffrey R. Livezey, Kevin K. Chung, Kevin S. Akers, Daniel J. Selig, Elaine D. Por |
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Rok vydání: | 2021 |
Předmět: |
Adult
Male Imipenem Burn injury Metabolic Clearance Rate Military Health Services Population Serum albumin 030226 pharmacology & pharmacy Monte Carlo simulations 03 medical and health sciences 0302 clinical medicine Pharmacometrics Pharmacokinetics antibiotic Humans burn Medicine Pharmacology (medical) Dosing education Serum Albumin Pharmacology Volume of distribution education.field_of_study biology business.industry Acute kidney injury Acute Kidney Injury Middle Aged medicine.disease Anti-Bacterial Agents 030220 oncology & carcinogenesis Anesthesia biology.protein Female Hemofiltration Burns business Monte Carlo Method pharmacokinetics medicine.drug |
Zdroj: | Journal of Clinical Pharmacology |
ISSN: | 1552-4604 0091-2700 |
Popis: | 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. |
Databáze: | OpenAIRE |
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