Metronidazole Pharmacokinetics Across Species: Meta-Analysis Integrating Allometric Scaling and Minimal Physiologically-Based Pharmacokinetic Modeling
Year: 2025
Type: article
Study designs: Systematic Review, Meta-Analysis
Abstract: Metronidazole (MTZ) is frequently used in both human and veterinary medicine to treat infections caused by certain protozoa and anaerobic bacteria. This study investigates the pharmacokinetic (PK) profiles of MTZ for available species in the literature by utilizing a linear, allometric, minimal physiologically-based PK (mPBPK) model. High quality PK data for intravenous (IV, n = 13) and oral (PO, n = 10) single doses were collected. Reported clearances ( CL ) and volumes of distribution ( V SS ) were highly correlated (R 2 = 0.957, 0.969) with body weights ( BW ) with allometric power coefficients of 0.97 and 0.87. A mPBPK model with one perfusion-limited tissue compartment was used to evaluate MTZ PK using anatomical and physiological parameters for each species. The mPBPK model adequately captured the IV PK profiles when using species-specific CL values and a generalized tissue:plasma partition coefficient ( K p = 0.792 (CV 2.76%)) except for sheep and goats that had very low K p values. The IV and PO profiles were best fitted jointly with shared physiological parameters and species-specific clearances, K p values (range 0.55 to 1.44, mean 0.86), and bioavailability (F 0.32 – 1.00, mean 0.73). Overall, successfully integrating allometric scaling into a mPBPK model for diverse species revealed very consistent disposition of MTZ with generally BW -proportional CL values, reasonably conserved K p values, and a moderate range of absorption rates and high bioavailability. Graphical Abstract
Source: The AAPS Journal
Authors: Fatma Kir, William J. Jusko
Language: English
Subfield: Small Animals
Field: Veterinary
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,090
Funder: National Institutes of Health
OpenAlex ID: W4417013901