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KMID : 0043320110340111939
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Archives of Pharmacal Research
2011 Volume.34 No. 11 p.1939 ~ p.1943
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Effects of Pluronic F68 and Labrasol on the intestinal absorption and pharmacokinetics of rifampicin in rats
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Ma Li
Wei Yuhui
Zhou Yan
Ma Xiaohua
Wu Xin’an
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Abstract
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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 highperformance 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 t1/2 (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 AUC0?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.
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KEYWORD
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Pluronic F68, Labrasol, Rifampicin, P-gpIntestinal absorption, Pharmacokinetics
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