POST-GRADUATE STUDENTS

Problem: Dietary botanicals are often consumed together with allopathic medicines. This may give rise to clinically significant pharmacokinetic interactions such as altered drug absorption. Not all in vivo pharmacokinetic interactions can reliably be predicted by in vitro means. However, in vitro intestinal models as useful predictive tools for identifying potentially significant botanical-drug interactions are needed. This study compared the effects of selected dietary botanical extracts on cimetidine transport across two in vitro intestinal models. Methods and Procedures: Bi-directional transport of cimetidine was measured across Caco-2 cell monolayers and excised pig jejunum tissue in the absence (negative control) and presence of verapamil (positive control) and in the presence of selected plant extracts (experimental groups). Main Findings: Sclerocarya birrea (marula) and Psidium guajava (guava) crude extracts significantly (p<0.05) decreased cimetidine efflux in both in vitro models resulting in increased absorptive movement of the drug. Crude extracts from Dovyalis caffra (Kei Apple), Prunus persica (peach), Aspalathus linearis (rooibos tea), Daucus carota (carrot), Prunus domestica (plum), Beta vulgaris (beetroot) and Fragaria x ananassa (strawberry) exhibited insignificant or inconclusive effects due to differences observed in the cimetidine transport between the two models. A higher efflux of cimetidine was obtained in the Caco-2 cell model than the pig intestinal model. In vitro pharmacokinetic interactions of the plant materials on cimetidine efflux were consequently much pronounced in the Caco-2 cell model than the pig intestinal model. Pharmacokinetic interactions caused by marula and guava fruits were significant. Conclusions: Caco-2 cells were more sensitive to the effects of investigated plant extracts and more permeable than pig jejunum tissue. The significant in vitro pharmacokinetic interactions identified in this study between the crude extracts and isolated fractions of two fruit (marula and guava) and cimetidine may be predictive of possible clinically significant interactions with drugs that are P-glycoprotein substrates, especially those with narrow therapeutic indices or high potencies. On the other hand, controlled herb-drug interactions via P-glycoprotein inhibition potentially present an opportunity for enhancing the permeability of orally administered drugs with poor bioavailabilities.