Pharmacokinetic Interactions Between Artemisinin-Based Combination Therapies and Commonly Co-Administered Nigerian Herbal Preparations: A Clinical Pharmacognosy Investigation

Concurrent use of artemisinin-based combination therapies (ACTs) and herbal preparations is widespread in Nigeria across all geopolitical zones, yet systematic clinical pharmacokinetic interaction data are almost entirely absent. The lack of this evidence base creates significant safety blind spots for malaria management, as pharmacokinetic herb-drug interactions could alter ACT plasma exposure and compromise therapeutic efficacy. This study conducts a multi-phase clinical pharmacognosy investigation of pharmacokinetic interactions between artemether-lumefantrine and three commonly co-administered Nigerian herbal preparations: Morinda lucida decoction, Carica papaya leaf extract, and a commercial polyherbal antimalarial. Phase 1 employs CYP450 enzyme phenotyping in a healthy volunteer crossover study to determine the effects of each herbal preparation on CYP3A4, CYP2D6, and CYP1A2 activity using validated probe substrates. Phase 2 conducts a prospective pharmacokinetic interaction study in uncomplicated P. falciparum malaria patients with documented concurrent herbal use at secondary health facilities in Enugu, Kano, and Ondo States. Full pharmacokinetic profiles (Cmax, AUC, t1/2, CL) of artemether, dihydroartemisinin, and lumefantrine were determined by validated LC-MS/MS methods. Phase 1 showed significant CYP3A4 induction by the polyherbal product, correlating with 34% reduction in lumefantrine AUC in Phase 2 concurrent users. Morinda lucida produced moderate CYP3A4 inhibition. These findings provide the first Nigerian-contextualised clinical evidence base for ACT herb interaction risks and recommend formal interaction warnings in ACT prescribing guidance. Keywords: artemether-lumefantrine, herb-drug interaction, CYP3A4, pharmacokinetics, clinical pharmacognosy