Chronopharmacology of Immunosuppressive Drugs in Canine Immune-Mediated Haemolytic Anaemia: Optimising Dosing Time in Tropical Nigeria

Chronopharmacology explores how circadian rhythms influence drug pharmacokinetics, pharmacodynamics, and toxicity, enabling optimised dosing time to maximise therapeutic benefit and minimise adverse effects. In immune-mediated haemolytic anaemia, immunosuppressive therapy with prednisolone, ciclosporin, and mycophenolate mofetil is the cornerstone of treatment, but the influence of dosing time on therapeutic outcomes in dogs in tropical West Africa has not been investigated. Circadian variation in immune function, cortisol secretion, and drug-metabolising enzyme activity may differ between Nigerian tropical dogs and temperate breed reference populations due to differences in ambient temperature, photoperiod, and lifestyle. This study characterised circadian variations in corticosterone, lymphocyte counts, and metabolic enzyme activities over 24 hours in 30 healthy mixed-breed dogs in Lagos, Ibadan, and Ife, South West Nigeria, and evaluated the pharmacokinetic and pharmacodynamic chronovariability of prednisolone administered at 08:00 and 20:00 hours in 40 dogs with confirmed immune-mediated haemolytic anaemia. Serial blood sampling over 24 hours was performed using indwelling catheters. Corticosterone showed a circadian nadir at 20:00 hours and peak at 06:00 hours, consistent with temperate patterns. Prednisolone pharmacokinetics showed significant chronovariability, with morning administration achieving higher Cmax and shorter Tmax. Therapeutic response assessed by PCV increase and reticulocyte count normalisation was significantly faster in dogs receiving morning administration. Evening dosing was associated with higher incidence of polydipsia and polyuria. These findings establish clinically relevant chronopharmacological principles for immunosuppressive therapy in canine IMHA under Nigerian tropical conditions, supporting morning dosing for optimal efficacy. Keywords: chronopharmacology, prednisolone, immune-mediated haemolytic anaemia, dogs, Lagos.