Influence Of A Herbal Antimalarial On The Disposition Of Amodiaquine In Mice Awodayo Oluwatoyin Adepiti
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Date
2013
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Abstract
The study evaluated the antimalarial efficacy of MAMA decoction, a multi-component herbal preparation, assessed the individual activities of the component plants and evaluated possible pharmacokinetic and pharmacodynamic interactions between MAMA decoction (MD) and amodiaquine (AQ). This was with a view to providing information on the potentials of MD as an indigenous antimalarial drug and the possible benefit or risk of concurrent administration of MD and AQ.
MD and the decoctions of its component plants (Alstonia boonei De Wild, Azadirachta indica A. Juss, Morinda lucida Benth and Mangifera indica L.) were prepared by established method, concentrated in vacuo and freeze-dried. The acute toxicity of MD was determined according to Lorke’s method while its antimalarial activity was evaluated by the early- and established- malaria infection test models. In the early malaria test, freeze-dried extracts of MD and those of the decoctions of its component plants, at doses of 15–240 mg/kg, were administered orally to Plasmodium berghei-infected mice for four days while for the established-infection test, MD(60-240 mg/kg) was orally administered to parasitized mice for five days. Giemsa-stained thin blood film, prepared from blood obtained from the tail of each mouse was microscopically assessed for parasite clearance levels. In both cases, amodiaquine (AQ, positive control) and distilled water (negative control) were similarly screened. Pharmacodynamic interactions between MD and AQ were investigated by oral administration of sub-therapeutic (1.25 mg/kg AQ and 30 mg/kg MD) and therapeutic (10 mg/kg AQ and 120 mg/kg MD) doses, both separately and in combination, using parasitized mice for the antimalarial test models. For the pharmacokinetic study, 216 mice were distributed into three groups of 72 mice each and AQ (10 mg/kg) was administered orally to each mouse in the first group while mice in the second group received a combination of AQ (10 mg/kg) and MD (120 mg/kg) each. Mice in the third group were pre-treated with MD (120 mg/kg) for three days prior to a single xix
dose administration of AQ (10mg/kg). Blood samples were obtained before and at predetermined intervals, followed by reversed-phase HPLC analysis.
The median lethal dose (LD50) of MD was found to be 3,807 mg/kg while the median effective doses (ED50) for the early malaria infection test were 43, 79, 140, 135, 208 and 3.9 mg/kg for MD, Alstonia boonei, Azadirachta indica, Morinda lucida, Mangifera indica and AQ, respectively. For the established infection test, MD at 240 mg/kg gave 54.5 % parasite clearance on day 5 post-treatment. A combination of sub-therapeutic doses of MD and AQ showed additive antimalarial effects while at therapeutic doses the combination gave 100 % clearance suggestive of a potentiation of the antimalarial activity of AQ. Pharmacokinetic analysis showed that the co-administration of MD and AQ resulted in increased half-life (t½) of AQ. The time to reach the maximum concentration (Tmax) and t½ of desethylamodiaquine (DAQ) increased by 8-fold and 106.7 %, respectively. The maximum concentration (Cmax) of AQ significantly increased (F=10.92; P=0.001) while its t½ reduced by 60 % on pretreatment with MD. Also, DAQ showed an 8-fold increase in its t½ while a non-significant (F=0.27; P=0.614) reduction was observed in the Cmax.
The study concluded that the ethnomedical antimalarial claim on MD is justified and that its combination with AQ may be safe and highly beneficial in view of possible future formulation as an antimalarial combination therapy in Man
Description
xii, 135p
Keywords
the antimalarial, herbal, multi-component, amodiaquine, decoctions, infection, Azadirachta indica, pharmacodynamic