Pharmacodynamic and Pharmacokinetic Limitations of Anti-protozoal drugs: A Comprehensive Review

Background: Protozoan ailments, such as leishmaniasis, Chagas disease, African trypanosomiasis, amoebiasis, and malaria, present social, economic challenges contributing significantly to global health burdens. Neglected Tropical Diseases (NTDs) encompass seventeen infectious maladies endemic in distinct developing nations, triggering significant morbidity and mortality, and perpetuating poverty. Effective remedies necessities potent therapeutic entities; however, Pharmacodynamic (PD) and Pharmacokinetic (PK) limitations impede the attainment of therapeutic efficacy. Objectives: The Current review explores PD and PK constraints of antiprotozoal drugs, focusing on challenges in efficacy, absorption, metabolism, as well as drug resistance. PD constraints: Target-site limitations, toxicity, and narrow therapeutic window, resistance mechanisms. These issues are further compounded by the toxicity and resistance observed with existing antiprotozoal agents. PK constraints: Drug-drug interactions, short shelf life, high clearance rate, poor drug distribution, and reduced bioavailability. Conclusion: Overcoming these limitations requires the development of novel antiprotozoal agents, including nanocarrier-based drug delivery systems, prodrug strategies, and combination therapies tailored through personalized medicine. Addressing PD along with PK constraints is pivotal in therapeutic success. The integration of advanced drug delivery systems, prodrug approaches, and nanotechnology with precision medicine can enhance efficacy, reduce toxicity, and mitigate drug resistance in antiprotozoal therapy.