Influence of MAMA decoction, an Herbal Antimalarial, on the Pharmacokinetics of Amodiaquine in Mice
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Background and Objective
MAMA decoction (MD) is an antimalarial product prepared from the leaves of Mangifera indica L. (Anacardiaceae), Alstonia boonei De Wild (Apocynaceae), Morinda lucida Benth (Rubiaceae) and Azadirachta indica A. Juss (Meliaceae). A previous report showed that MD enhanced the efficacy of amodiaquine (AQ) in malaria-infected mice, thus suggesting a herb–drug interaction. The present study hence evaluated the effect of MD on the disposition of AQ in mice with a view to investigating a possible pharmacokinetic interaction.
In a 3-period study design, three groups of mice (n = 72) were administered oral doses of AQ (10 mg/kg/day) alone, concurrently with MD (120 mg/kg/day), and in the 3rd period, mice were given AQ after a 3-day pre-treatment with MD. Blood samples were collected between 0 and 96 h for quantification of AQ and its major metabolite, desethylamodiaquine, by a validated high-performance liquid chromatography method.
Maximum concentrations of AQ increased by 12% with the concurrent dosing of MD and by 85% in the group of mice pre-treated with MD. The exposure and half-life of desethylamodiaquine increased by approximately 11% and 21%, respectively, with concurrent administration. Corresponding increases of approximately 20% and 33% of desethylamodiaquine were also observed in mice pre-treated with MD.
MD influenced the pharmacokinetics of AQ and desethylamodiaquine, its major metabolite. The increase in the half-life and systemic exposure of AQ following its co-administration with MD may provide a basis for the enhanced pharmacological effect of the combination in an earlier study in Plasmodium-infected mice.
AOA is grateful to the Obafemi Awolowo University (OAU), Nigeria, for support under the Staff Development Programme. The OAU Research Committee is acknowledged for Grant 11813AFL. The authors are grateful to the Carnegie Foundation/Therapeutic Drug Monitoring Laboratory, OAU Teaching Hospitals Complex, Ile-Ife, Nigeria for the high-performance liquid chromatography facility.
Compliance with Ethical Standards
Support for the study was provided by the Obafemi Awolowo University, Ile-Ife, Nigeria under the Staff Development Programme and the University Research Committee Grant 11813AFL.
Conflict of interest
The authors declare no conflict of interest.
Approval for the study was obtained from the Health Research Ethics Committee of the Obafemi Awolowo University, Ile-Ife, Nigeria (IPHOAU/12/90). “The Guide for the care and use of laboratory animals” was strictly followed.
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