College of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Arch Pharm Res. 2011 Nov;34(11):1939-43. doi: 10.1007/s12272-011-1114-z. Epub 2011 Dec 3.
The aim of this study was to investigate the effects of Pluronic F68 and Labrasol on the intestinal absorption and pharmacokinetics of rifampicin. Intestinal permeability of rifampicin with or without excipients was evaluated by an in situ single-pass perfusion method. A high-performance liquid chromatographic method was applied to study the pharmacokinetics of rifampicin with or without excipients. Labrasol or Pluronic F68 (0.1% and 0.05%, v/v), co-perfused with rifampicin (60 μg/mL), significantly increased in situ permeability. Similarly, verapamil (a typical P-gp inhibitor) also increased in situ permeability, but to a lesser extent. In vivo, the oral administration of rifampicin with or without Pluronic F68, Labrasol or verapamil resulted in statistically significant effect on t(1/2) (4.83 to 7.75, 6.42 and 7.46 h) and total body clearance (0.46 to 0.26, 0.28, 0.24 L/h/kg). In addition, Pluronic F68, Labrasol and verapamil produced minor changes in AUC(0-t), which improved 1.55-, 1.54-, and 1.73-fold in comparison to control group, respectively. These results showed that Labrasol and Pluronic F68 might inhibit the function of P-gp in the intestine, thereby increasing intestinal absorption and changing the pharmacokinetic parameters of rifampicin. Therefore, excipient selection is an important factor to consider in rational formulation design.
本研究旨在探讨 Pluronic F68 和 Labrasol 对利福平肠道吸收和药代动力学的影响。采用原位单次灌流法评价利福平有无辅料时的肠道通透性。采用高效液相色谱法研究有无辅料时利福平的药代动力学。Labrasol 或 Pluronic F68（0.1%和 0.05%，v/v）与利福平（60μg/mL）共灌流时，可显著增加原位通透性。同样，维拉帕米（一种典型的 P-糖蛋白抑制剂）也增加了原位通透性，但程度较小。体内，利福平与 Pluronic F68、Labrasol 或维拉帕米同时给药，对 t(1/2)（4.83 至 7.75、6.42 和 7.46 h）和全身清除率（0.46 至 0.26、0.28、0.24 L/h/kg）有统计学显著影响。此外，Pluronic F68、Labrasol 和维拉帕米使 AUC(0-t)略有变化，与对照组相比分别提高了 1.55、1.54 和 1.73 倍。这些结果表明，Labrasol 和 Pluronic F68 可能抑制了肠道中的 P-糖蛋白的功能，从而增加了肠道吸收并改变了利福平的药代动力学参数。因此，辅料的选择是合理配方设计中需要考虑的重要因素。
