An Original Framework for Personalised Antifungal Pharmacotherapy in Invasive Fungal Infections in Immunocompromised Nigerian Patients

Invasive fungal infections carry high mortality in immunocompromised Nigerian patients, and the pharmacokinetic variability of antifungal agents in this population, compounded by drug interactions with antiretroviral and immunosuppressant therapies, makes standard dosing inadequate for many patients. This study developed an original framework for personalised antifungal pharmacotherapy in immunocompromised Nigerian patients with invasive fungal infections. A comprehensive multi-stage research programme was conducted at teaching hospitals in Lagos, Ibadan, and Port Harcourt. A prospective pharmacokinetic study characterised fluconazole, voriconazole, and caspofungin dispositions in 80 immunocompromised patients stratified by HIV status, solid organ transplant, and haematological malignancy. Population pharmacokinetic models were developed in NONMEM incorporating disease-specific covariates and drug interaction parameters. Monte Carlo simulations evaluated target attainment probability for different dosing regimens against common Candida and Cryptococcus species MIC distributions from Nigerian clinical isolate databases. Voriconazole pharmacokinetics demonstrated the highest inter-patient variability (CV 78 percent), with CYP2C19 polymorphisms and azole-antiretroviral interactions as dominant sources. A personalised dosing algorithm integrating model-predicted optimal exposures, patient covariate data, and available TDM results was developed and evaluated through clinical simulation. The algorithm improved therapeutic target attainment by 34 percent versus standard dosing in the simulation study. The framework constitutes an original contribution to antifungal pharmacotherapy science in immunocompromised African patients.

Keywords: antifungal pharmacotherapy, personalised dosing, invasive fungal infections, immunocompromised patients, Nigeria