Moringa oleifera leaf powder alters the pharmacokinetics of amodiaquine in healthy human volunteers.

WHAT IS KNOWN AND OBJECTIVE: Moringa oleifera (MO) Lam (Moringaceae) is commonly used as food supplement and as medicine in most African countries where malaria is also endemic. Therefore, co-administration of MO with antimalarials is a possibility. This study investigated the effects of MO leaves powder on the pharmacokinetics of amodiaquine (AQ) in human subjects. METHODS: Twenty healthy volunteers were recruited for the 3-period study. In the first period, a single dose of AQ tablet (10 mg/kg) was administered orally after an overnight fast. After a 7-day washout period, AQ was co-administered with MO. For the third period, each subject took 3 g MO once daily for 7 days and on the 8th day, MO was co-administered with AQ. The plasma concentrations of amodiaquine and desethylamodiaquine (DEAQ) were simultaneously determined using a validated HPLC method. RESULTS AND DISCUSSION: The results showed a significant decrease (P = .037) in the Cmax of AQ after concurrent administration (CA) with MO, whereas after pretreatment (PT), there was a 32% decrease in the Cmax of AQ. For the metabolite, DEAQ, Cmax increased significantly (P = .006) by 79.36%, and Cmax in PT was significantly higher than (P = .001) that of the CA arm of the study. AUC of DEAQ increased significantly by 40.4% (P = .006) and by 188% (P = .001) after CA and PT, respectively. WHAT IS NEW AND CONCLUSION: The study established pharmacokinetic interaction between AQ and MO when given together or following a long period of ingestion of MO. This may have clinical implications for malaria therapy.

Influence of CYP3A5*3 and ABCB1 C3435T on clinical outcomes and trough plasma concentrations of imatinib in Nigerians with chronic myeloid leukaemia.

WHAT IS KNOWN AND OBJECTIVE: Imatinib mesylate is the first-line drug for the treatment of Philadelphia/bcr-abl positive chronic myeloid leukaemia (CML). It is known to be metabolized mostly by CYP3A4 and CYP3A5 isoforms while its efflux is mediated by the transporters ABCB1 and ABCG2. Genetic polymorphism of some of these enzymes and transporters have been linked with inter-individual variations in the pharmacokinetics of the drug. This study, therefore, investigated the influence of CYP3A5*3, ABCG2 421C>A and ABCB1 3435 C>T genetic polymorphism on the clinical outcome and steady-state trough plasma concentration (TPC) of imatinib in Nigerians with CML. METHODS: A total of 110 Nigerians with CML each of whom had been receiving a 400 mg daily dose of imatinib for at least 1 month were genotyped for CYP3A5*3, ABCG2 421C>A and ABCB1 3435 C>T. The TPC of all the patients were determined by a validated HPLC method and possible relationships between genotypes, age, clinical outcome, sex, TPC and ethnicity were analysed. RESULTS AND DISCUSSION: Subjects of TT genotype of ABCB1 C3435T had higher frequencies of complete haematological response (CHR), complete cytogenetic response (CCR) and major molecular response (MMR) but these were not statistically significant (P < 0·05). No genetic polymorphism in ABCG2 421C>A was observed. However, significant associations were observed between TPC and various genotypes in both CYP3A5*3 (P < 0·001) and ABCB1 C3435T (P < 0·001). The GG and TT genotypes in CYP3A5*3 and ABCB1 C3435T, respectively, were linked with higher TPC. WHAT IS NEW AND CONCLUSION: This is the first pharmacogenetics study of CML patients in the Nigerian population with ethnic differences in the distribution of ABCB1 C3435T. Genetic polymorphisms in CYP3A5*3 and ABCB1 C3435T are associated with TPC in CML patients in this population.