MAMA Decoction, an herbal antimalarial preparation, alters the disposition of amodiaquine in humans

MAMA decoction (MD), a preparation from the leaves of Mangifera indica, Alstonia boonei, Morinda lucida, and Azadirachta indica, was co-administered with amodiaquine, and resulted in the synergistic clearance of malaria parasites in a previous report [1]. The pharmacokinetic basis for this observation, significant increases in the exposure and half-life of desethylamodiaquine, the major metabolite of amodiaquine, was reported in mice [2]. Here, a further evaluation of these previously identified herb-drug interactions was carried out in healthy human volunteers.

Single oral doses of amodiaquine (10 mg/kg) with/without MD (0.25 L, 0.04% w/v gedunin) were co-administered to 16 healthy volunteers in a three-period crossover design. Blood samples were collected between 0 h and 48 h for each study period and analysed for amodiaquine and desethylamodiaquine contents. The effect of MD on amodiaquine disposition across study periods was investigated using a non-linear mixed-effect pharmacokinetic model which estimated population parameters with the stochastic approximation expectation maximization (SAEM) algorithm implemented in Monolix 2020R1.

The disposition of amodiaquine and desethylamodiaquine were each described, adequately, by two- and one-compartment structural models respectively, and a first-order oral absorption rate. The co-administration of amodiaquine with MD resulted in about 41% decrease in the apparent volume of distribution of amodiaquine (VAQ/F). Chronic administration of MD prior to the dosing of amodiaquine led to a 22% decrease in VAQ/F.

MD appeared to decrease the tissue partitioning of amodiaquine in humans. The consequence of this for effective parasite clearance in humans is, however, unknown.

The authors declare no conflict of interest.

• References

• 1 Adepiti AO, Elujoba AA, Bolaji OO. Evaluation of herbal antimalarial MAMA decoction-amodiaquine combination in murine malaria model. Pharm Biol 2016; 54: 2298-2303
• 2 Adepiti AO, Adeagbo BA, Adehin A. et al. Influence of MAMA decoction, an herbal antimalarial, on the pharmacokinetics of amodiaquine in mice. Eur J Drug Metab Pharmacokinet 2020; 45: 81-88

Publication History

Article published online:
12 December 2022