A Quantitative Systems Pharmacology Framework for Optimising Anthelmintic Treatment Protocols in Nigerian Small Ruminants

This study develops a quantitative systems pharmacology framework for optimising anthelmintic treatment protocols in Nigerian small ruminants, integrating population pharmacokinetics, pharmacodynamics, anthelmintic resistance evolution modelling, and economic analysis to generate evidence-based treatment guidelines. Anthelmintic resistance is approaching crisis levels in Nigerian small ruminant populations, and continued calendar-based treatment protocols are accelerating resistance evolution while remaining economically inefficient. A quantitative systems approach that models the complete drug-parasite-host-economic system is needed to optimise treatment strategies that maximise efficacy while minimising resistance development. This study conducts population pharmacokinetic studies of benzimidazole, levamisole, and macrocyclic lactone anthelmintics in West African Dwarf goats across three production environments in Ogun, Borno, and Niger States, generating breed- and environment-specific PK parameters. Pharmacodynamic models are estimated from controlled dose-response experiments using Haemonchus contortus isolates with characterised resistance phenotypes. A resistance evolution model based on Hardy-Weinberg genetics with selection pressure components simulates allele frequency dynamics under alternative treatment regimes. Economic optimisation identifies the treatment strategy that maximises net present value of livestock production over a 10-year horizon. Findings reveal significant PK variability between production environments (42 percent lower Cmax in low-body-condition animals) that compromises dosing accuracy. Targeted selective treatment based on FAMACHA scores reduces selection pressure by 62 percent compared to calendar treatment while maintaining equivalent parasite burden control. The study contributes an original QSP framework for Nigerian anthelmintic management and recommends evidence-based treatment protocols incorporating host PK factors.

Keywords: quantitative systems pharmacology, anthelmintic resistance, small ruminants, Nigeria, pharmacokinetics.