Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia.
Eur J Nutr. 2010 Sep;49(6):373-84. doi: 10.1007/s00394-010-0095-x. Epub 2010 Feb 7.
Disease preventing effects gained by garlic consumption have been recognized since early period of history, making commercially available garlic supplements attractive to the general public. Possible pharmacokinetic interactions which could occur between applied drugs and aged garlic extract (AGE) are unknown.
To test in vitro impact of some garlic phytochemicals on P-glycoprotein (Pgp), the most recognized efflux transporter, and the effect of AGE on passive membrane permeability, absorptive and secretory intestinal transporters.
Rat small intestine and Caco-2 cell monolayers, mounted in side-by-side diffusion chambers were used.
Hydrophilic sulphur compounds increased Pgp mediated Rhodamine 123 (Rho123) efflux, whereas the lipophilic ones increased Pgp efflux through rat ileum but not through Caco-2 cell monolayers. Increased activities of secretory (Pgp, multidrug-resistance associated protein 2) and absorptive (monocarboxylate transporter 1, organic anion transporting polypeptide) transporters involved in drug absorption were observed in rat small intestine and Caco-2 cell monolayers in the presence of AGE. Transport of drugs mediated by breast cancer resistance protein and H(+)-oligopeptide transporter 1 was activated in rat intestine but inhibited through Caco-2 cells. Passive membrane permeability of tested compounds remained unaltered through rat small intestine, while significant changes were observed with Caco-2 cell monolayers.
Due to the observed in vitro pharmacokinetic interactions between AGE and investigated cardiovascular, antidiabetic and antiviral drugs, in vivo absorption changes are possible, but the magnitude of change depends on the most profound process involved (influx, efflux, passive diffusion) in compounds permeability.
早在历史早期，人们就认识到大蒜摄入具有预防疾病的功效，这使得市售大蒜补充剂对公众具有吸引力。目前尚不清楚应用药物与陈年大蒜提取物（AGE）之间可能发生的药代动力学相互作用。
在体外测试一些大蒜植物化学物质对 P 糖蛋白（Pgp）的影响，Pgp 是最被认可的外排转运蛋白，以及 AGE 对被动膜通透性、吸收性和分泌性肠转运蛋白的影响。
使用安装在侧流扩散室中的大鼠小肠和 Caco-2 细胞单层。
亲水性硫化合物增加了 Pgp 介导的罗丹明 123（Rho123）外排，而疏水性硫化合物则通过大鼠回肠增加了 Pgp 外排，但未通过 Caco-2 细胞单层。在 AGE 存在的情况下，观察到参与药物吸收的分泌型（Pgp、多药耐药相关蛋白 2）和吸收型（单羧酸转运蛋白 1、有机阴离子转运多肽）转运体的活性增加在大鼠小肠和 Caco-2 细胞单层中。乳腺癌耐药蛋白和 H（+）-寡肽转运蛋白 1 介导的药物转运在大鼠肠道中被激活，但在 Caco-2 细胞中被抑制。测试化合物对大鼠小肠的被动膜通透性保持不变，而在 Caco-2 细胞单层中则观察到显著变化。
由于观察到 AGE 与研究的心血管、抗糖尿病和抗病毒药物之间的体外药代动力学相互作用，因此可能会发生体内吸收变化，但变化的幅度取决于化合物渗透性涉及的最主要过程（内流、外流、被动扩散）。
