Evaluation of the interaction between the ethanol pulp extract of Chrysophyllum albidum and Artemether/ Lumefantrine

Objective: Though Chrysophyllum albidum has antimalarial and antioxidant property, it is commonly consumed as a fruit in the South East Nigeria. There could be possible pharmacodynamics and pharmacokinetics interaction if the fruit is consumed while on malaria treatment with artemether-lumefantrine.

The study was designed to investigate the possible enhancement of the antimalarial potency as well as possible herb-drug interaction resulting from concurrent administration of artemeter-lumefantrine and Chrysophyllum albidum.

Materials and methods: Combinations of artemeter-lumefantrine and Chrysophyllum albidum were investigated in Antiplasmodial activity using curative test procedure. Forty mice were infected with P. berghei-infected red blood cells by intraperitoneal injection. The animals (23-27g, 5-6 weeks old) were divided into 8 groups (n=5). There were treated with 250 mg/kg, 500 mg/kg and 1000 mg/kg of the extract in combination with 20 mg/120 mg of artemether-lumefantrine. The parasitemia level was determined by counting the number of parasitized erythrocytes in random fields of the microscope. The effect of Chrysophyllum albidum on the pharmacokinetics of Artemether-lumefantrine (A/L) in mice was studied in three phases. Each phase was done utilizing a total of 30 rats assigned to 5 groups of 6 animals to which was administered A/L and/or the plant extract orally, after an overnight fast, with feeding and access to water resuming 2 h after drug administration. Concentration of artemether-lumefantine was determined using modified validated liquid chromatography assay.

Results: The combination of the pulp extract and Artemether-lumefantrine at tested doses of 250, 500 and 1000 mg/kg produced significant (p< 0.05, 0.01 and 0.001), dose dependent parasitaemia suppression (88.81, 94.58 and 100%) compared to the negative control group. The plasma concentration of Chrysophyllum albidum +Artemether-lumefantrine had a concentration of (56 ng/mg) at 30 minutes. The overall systemic exposure of AL, represented by the AUC, increased by 56.05% when CAL was concurrently administered and by 296.97% when the mice were pre-treated with the decoction.

Conclusion: Chrysophyllum albidum extract has a potential to increase the antimalaria property of Artemether-lumefantrine due to probable inhibitory effect on Artemether-lumefantrine metabolism by Chrysophylum albidum. The pharmacokinetics of Artemether-lumefantrine like systemic exposure and half-life were also affected by Chrysophylum albidum.