Antimalaria Activity of Caffeine, Orally Administered with a Lipid-Based Formulation in a Murine Model

Abstract Despite Caffeine being known essentially for its psychoactive properties, an attempt was made in this study to investigate its potential antimalarial activity considering that it’s an alkaloid and that the malaria parasite is a purine auxotroph. In the baseline experiment, caffeine was administered at three doses (5, 10 and 20 mg/kg) once daily in suppressive and curative models. The observed chemosuppression activity was comparable to that of chloroquine (CQ) in both experiments. In the baseline suppressive experiment, a chemosuppression of 70.39% for CQ (at 10 mg/kg) was observed, while caffeine had 78.90%, 80.73% and 81.95% at the respective doses. However, the survival index estimated based on the rate of survival of the experimental animals for 28 days post infection, was very low (the same trend was observed in the baseline curative experiment). This initial result showed that caffeine had potential as an antimalarial agent relative to the standard drug, chloroquin, and the lipid-based formulation must have played a role in ensuring that the caffeine had enhanced bioavailability. A follow-up experiment was conducted in which the caffeine was administered twice daily (at 20 mg/kg) in suppressive and curative experiments. The observed chemosuppression in the suppressive test (with twice daily administration), showed that caffeine at 20 mg/kg had similar antiplasmodial activity with chloroquine (10 mg/kg). Both had chemosuppression of 53.6% and 54.36% respectively and a survival index of 100% was recorded for both compounds. The curative experiment that followed (also with twice daily administration) further showed that caffeine compares favourably with chloroquine. Caffeine exhibited 45.92%, 72.00%, 69.87% chemosuppression as compared to chloroquine with 20.97%, 65.64%, 60.95% for 3, 5 and 7 days of treatment respectively. Caffeine’s survival index was very high and much better than what was observed in the once daily administration experiment. A survival index of 93% was observed in the twice daily administration curative experiment against the 53% survival index observed in the once daily curative experiment. It is assumed that apart from the fact that the lipid-based oral delivery system ensured that the caffeine was effectively absorbed, bypassing liver first-pass, the twice daily administration also helped to sustain large concentrations of the caffeine in the blood to offset the rapid clearance that caffeine is known for.