Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Grahamstown, South Africa.
J Pharm Pharm Sci. 2012;15(2):221-33. doi: 10.18433/j3ns3x.
African traditional medicinal plants, such as Sutherlandia frutescens have the potential to interact pharmacokinetically with the protease inhibitor class of antiretrovirals, thereby impacting on their safety and efficacy. The effects of extracts and phytochemical components of Sutherlandia frutescens, on the in vitro absorption and metabolism of the protease inhibitor, atazanavir were thus investigated.
Aqueous and methanolic extracts of Sutherlandia frutescens were prepared by freeze-drying of hot water and methanol decoctions of Sutherlandia frutescens plant material respectively, whilst crude triterpenoid glycoside and flavonol glycoside fractions were isolated by solvent extraction and subsequent column chromatography. Atazanavir was quantitated in the absence or presence of these compounds as well as commercially available purported constituents of Sutherlandia frutescens, namely, L-canavanine, L-GABA and D-pinitol, after a one hour co-incubation in Caco-2 cell monolayers and human liver microsomes.
The triterpenoid and flavonol glycoside fractions were found to be present in the aqueous and methanolic extracts of Sutherlandia frutescens and were shown to contain the sutherlandiosides and sutherlandins known to be present in Sutherlandia frutescens. The aqueous extract and D-pinitol significantly reduced atazanavir accumulation by Caco-2 cells, implying a decrease in atazanavir absorption, whilst the opposite was true for the triterpenoid glycoside fraction. Both the aqueous and methanolic extracts inhibited atazanavir metabolism in human liver microsomes, whilst enhanced atazanavir metabolism was exhibited by the triterpenoid glycoside fraction.
The extracts and phytochemical components of Sutherlandia frutescens influenced the accumulation of atazanavir by Caco-2 cells and also affected ATV metabolism in human liver microsomes. These interactions may have important implications on the absorption and metabolism and thus the overall oral bioavailability of atazanavir.
非洲传统药用植物，如南非钩麻，有可能与抗逆转录病毒的蛋白酶抑制剂类药物发生药物动力学相互作用，从而影响其安全性和疗效。因此，研究了南非钩麻的提取物和植物化学成分对蛋白酶抑制剂阿扎那韦在体外吸收和代谢的影响。
通过冷冻干燥分别制备南非钩麻的水提物和甲醇提物，同时通过溶剂提取和随后的柱色谱分离粗三萜糖苷和黄酮醇糖苷级分。在 Caco-2 细胞单层和人肝微粒体中共同孵育 1 小时后，检测这些化合物以及南非钩麻中商业上可获得的据称成分 L-瓜氨酸、L-GABA 和 D-松醇在不存在或存在阿扎那韦时的含量。
发现三萜糖苷和黄酮醇糖苷级分存在于南非钩麻的水提物和甲醇提物中，并且含有已知存在于南非钩麻中的 sutherlandiosides 和 sutherlandins。水提物和 D-松醇显著降低了 Caco-2 细胞中阿扎那韦的积累，这意味着阿扎那韦的吸收减少，而三萜糖苷级分则相反。水提物和甲醇提物均抑制了人肝微粒体中阿扎那韦的代谢，而三萜糖苷级分则增强了阿扎那韦的代谢。
南非钩麻的提取物和植物化学成分影响了 Caco-2 细胞中阿扎那韦的积累，也影响了人肝微粒体中阿扎那韦的代谢。这些相互作用可能对阿扎那韦的吸收和代谢，从而对其整体口服生物利用度产生重要影响。
