Population pharmacokinetics of rifampin in the treatment of Mycobacterium tuberculosis in Asian elephants

E. F. Egelund; R. Isaza; A. P. Brock; A. Alsultan; G. An; C. A. Peloquin

doi:10.1111/jvp.12156

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Population pharmacokinetics of rifampin in the treatment of Mycobacterium tuberculosis in Asian elephants

Journal article

Open access

Peer reviewed

Population pharmacokinetics of rifampin in the treatment of Mycobacterium tuberculosis in Asian elephants

E. F. Egelund, R. Isaza, A. P. Brock, A. Alsultan, G. An and C. A. Peloquin

Journal of veterinary pharmacology and therapeutics, Vol.38(2), pp.137-143

04/01/2015

DOI: 10.1111/jvp.12156

PMID: 25236765

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Abstract

The objective of this study was to develop a population pharmacokinetic model for rifampin in elephants. Rifampin concentration data from three sources were pooled to provide a total of 233 oral concentrations from 37 Asian elephants. The population pharmacokinetic models were created using Monolix (version 4.2). Simulations were conducted using ModelRisk. We examined the influence of age, food, sex, and weight as model covariates. We further optimized the dosing of rifampin based upon simulations using the population pharmacokinetic model. Rifampin pharmacokinetics were best described by a one-compartment open model including first-order absorption with a lag time and first-order elimination. Body weight was a significant covariate for volume of distribution, and food intake was a significant covariate for lag time. The median C-max of 6.07g/mL was below the target range of 8-24g/mL. Monte Carlo simulations predicted the highest treatable MIC of 0.25g/mL with the current initial dosing recommendation of 10mg/kg, based upon a previously published target AUC(0-24)/MIC>271 (fAUC>41). Simulations from the population model indicate that the current dose of 10mg/kg may be adequate for MICs up to 0.25g/mL. While the targeted AUC/MIC may be adequate for most MICs, the median C-max for all elephants is below the human and elephant targeted ranges.

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Science & Technology

Veterinary Sciences

Details

Title: Subtitle: Population pharmacokinetics of rifampin in the treatment of Mycobacterium tuberculosis in Asian elephants
Creators: E. F. Egelund - University of Florida
R. Isaza - University of Florida
A. P. Brock - University of Florida
A. Alsultan - University of Florida
G. An - University of Florida
C. A. Peloquin - University of Florida
Resource Type: Journal article
Publication Details: Journal of veterinary pharmacology and therapeutics, Vol.38(2), pp.137-143
DOI: 10.1111/jvp.12156
PMID: 25236765
NLM abbreviation: J Vet Pharmacol Ther
ISSN: 0140-7783
eISSN: 1365-2885
Publisher: Wiley
Number of pages: 7
Language: English
Date published: 04/01/2015
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984366036602771

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