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Imatinib has been successful in the management of chronic myeloid leukemia (CML) but some patients experience adverse reactions or develop resistance to its use. The roles of some polymorphisms in genes encoding enzymes critical for the biotransformation of imatinib have been previously examined. This study, hence, evaluated some other unstudied functionally significant polymorphisms in CYP1A2, CYP2C8, CYP2C9, and CYP3A5. Trough imatinib blood levels and genotypes were determined in 42 CML patients by an HPLC-UV technique and a Sequenom iPLEX assay, respectively. Statistical analysis of the influence of genetic polymorphisms on standardized trough level detected no significant relationship. However, higher trough levels were observed in two homozygous carriers of CYP2C8*2 while diminished imatinib levels were seen in two homozygous carriers of CYP3A5*7. The study findings suggest that polymorphisms in drug metabolizing enzymes may be significant for imatinib therapy only in instances where all copies of the relevant studied genes are functionally impaired. [ABSTRACT FROM AUTHOR]

Context: Co-administration of amodiaquine with MAMA decoction (MD), an herbal antimalarial drug comprising the leaves ofMangifera indicaL. (Anacardiaceae), Alstonia booneiDe Wild (Apocynaceae), Morinda lucidaBenth (Rubiaceae) andAzadirachta indicaA. Juss (Meliaceae) was investigated. The practice of concurrent administration of herbal medicines with orthodox drugs is currently on the increase globally. Objective: 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 MAMA decoction with amodiaquine (AQ). Materials and methods: Combinations of MD with AQ were investigated in chloroquine (CQ)-sensitivePlasmodium bergheiNK 65 in varying oral doses (mg/kg) at: sub-therapeutic [MD30 + AQ1.25], therapeutic [MD120 + AQ10] and median effective [MD40 + AQ3.8], using chemosuppressive and curative antimalarial test models. Secondly,P. bergheiANKA (CQ-resistant)-infected mice were orally treated with MD 120, 240, [MD120 + AQ10] and [MD240 + AQ10] mg/kg, using both models. The survival times of mice were monitored for 28 d. Results: ED50values of MD and AQ were 48.8 and 4.1 mg/kg, respectively. A total parasite clearance of CQ-sensitiveP. bergheiNK65 was obtained with the therapeutic combination dose in the curative test giving an enhanced survival time. In CQ-resistantP. bergheiANKA-infected mice, [MD120 + AQ10] and [MD240 + AQ10] mg/kg gave comparable activities with AQ (10 mg/kg) in both models. Conclusion: The therapeutic combination dose gave total parasite clearance of CQ-sensitiveP. bergheiNK65, whereas none of the doses tested showed notable activity against CQ-resistantP. bergheiANKA. [ABSTRACT FROM PUBLISHER]