In vivo pharmacodynamic and pharmacokinetic interactions of Hibiscus sabdariffa calyces extracts with simvastatin.

WHAT IS KNOWN AND OBJECTIVES: Increasing number of patients use herbs with their medications. Such practice may result in beneficial or harmful herb-drug interactions. A recent survey reported that some participants co-administered Hibiscus sabdariffa, a widely used beverage, or tea, with their antihyperlipidaemic medications. This study therefore evaluated the effect of concomitant administration of Hibiscus sabdariffa calyces' extracts with simvastatin on hyperlipidaemia and pharmacokinetics of the drug in vivo. METHODS: Factorial experimental designs were used to evaluate the comparative effectiveness and interactions between simvastatin and aqueous extract of Hibiscus sabdariffa (AEHS) on lipid profile parameters in hyperlipidaemia-induced Wistar rats. Different combinations of low (AEHS 250 mg/kg; simvastatin 10 mg/kg) and high doses (AEHS 500 mg/kg; simvastatin 20 mg/kg) were administered individually and concurrently daily for 2 and 4 weeks. Lipid profile parameters were assessed at these treatment periods. Subsequently, the effect of aqueous beverage of Hibiscus sabdariffa (ABHS) on the pharmacokinetics of single-dose 40 mg simvastatin was also evaluated in six healthy human volunteers using two-period randomized crossover design. Blood samples were collected at predetermined times for 24 hours. The plasma obtained was analysed for simvastatin using RP-HPLC/UV method. RESULTS: Aqueous extract of Hibiscus sabdariffa reduced total cholesterol (Tc ) better than simvastatin (P = .031). Low-dose AEHS and low-dose simvastatin used concomitantly caused 38.3% and 57.4% reductions in Tc and triglyceride levels, respectively, compared with low-dose simvastatin (P < .05). Also, ABHS increased clearance and reduced peak concentration of simvastatin by 44.6% and 18.0%, respectively (P < .05). The geometric mean ratio of simvastatin AUC0-∞ with or without ABHS was 0.646 with the 90% confidence interval (0.564, 0.758) falling outside the bioequivalent range. WHAT IS NEW AND CONCLUSION: Aqueous extract of Hibiscus sabdariffa lowered Tc better than simvastatin and enhanced the antihyperlipidaemic activity of the drug when co-administered at low doses in an animal model. However, aqueous beverage of Hibiscus sabdariffa caused a significant herb-drug interaction resulting in overall reduction in exposure to simvastatin in humans. Caution should thus be placed on clinical judgement or recommendations based on the animal results. Nevertheless, co-administration of the beverage with simvastatin should be discouraged until more clinical data are available.

Influence of a Nigerian honey on CYP3A4 biotransformation of quinine in healthy volunteers.

WHAT IS KNOWN AND OBJECTIVES: Some studies, howbeit with conflicting reports, have suggested that consumption of honey has a potential to modulate drug metabolizing enzymes which may result in a honey-drug interaction. Numerous studies have established that honey varies in composition, influenced by the dominant floral, processing and environmental factors. Thus, variation in honey composition may be a contributing factor to the controversial results obtained. No previous drug interaction study has been carried out with any honey from Africa. CYP 3A4 is an important enzyme in drug metabolism studies as it is involved in the metabolism of over 50% of drugs in clinical use and quinine remains very relevant in malaria treatment in the tropics, and we therefore determined whether there is potential drug interaction between a Nigerian honey and quinine, a drug whose metabolism to 3-hydroxyquinine is mediated majorly by CYP3A4. METHODS: In a three-phase randomized crossover study with a washout period of 2 weeks between each treatment phase, ten (10) healthy volunteers received quinine sulphate tablet (600 mg single dose) alone (phase 1) or after administration of 10 ml of honey (Phase 2) and 20 mL of honey (Phase 3) twice daily for seven (7) days. Blood samples were collected at the 16th hour post-quinine administration in each phase, and quinine and its major metabolite, 3-hydroxyquinine, were analysed using a validated HPLC method. RESULTS: After scheduled doses of honey, the mean metabolic ratios of quinine (3-hydroxyquinine/quinine) increased by 24·4% (with 10 mL of honey) and reduced by 23·9% (with 20 mL of honey) when compared to baseline. These magnitudes of alteration in the mean metabolic ratios were not significant (P > 0·05; Friedman test). The geometric mean (95% CI) for the metabolic ratio of quinine before and after honey intake at the two dose levels studied was 0·82 (0·54, 1·23) and 1·29 (0·96, 1·72), respectively, and were also not significant (P = 0·296 and 0·081 respectively; Student's t-test). WHAT IS NEW AND CONCLUSION: This is a pioneer study on the effect of Nigerian/African honey on quinine metabolism. The findings indicated that low and high doses of honey did not significantly affect metabolism of quinine to 3-hydroxyquinine. This suggests that CYP3A4 activity is not significantly altered following low or high dose of honey, as CYP3A4 has been reported to be responsible for the conversion of quinine to 3-hydroxyquinine. In conclusion, the outcome of this study suggests that there may be no potential significant metabolic interaction between Nigerian honey and quinine administration.