Effects of Pluronic F68 and Labrasol on the intestinal absorption and pharmacokinetics of rifampicin in rats

Abstract

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.

Visualization of Time-Dependent Distribution of Rifampicin in Rat Brain Using MALDI MSI and Quantitative LCMS/MS

“…In plasma, RIF reached a C max of 7,952.90 ng/mL after a T max of 60 min, which is in accordance with lower values of several studies. [24][25][26][27] In the lung, the C max was 3,110.38 ng/mL with a similar T max of 60 min. Curves for both the plasma and lung concentrations showed similar trends, where there were steady initial increases in drug concentrations followed by a gradual decrease until trough concentrations were reached at 240 min.…”

Herb–Drug Interaction of Red Ginseng Extract and Ginsenoside Rc with Valsartan in Rats

“…Based on the similarity in the structure and protein binding features between rats and human and inhibitory effect on OATP transporters of Rb1, Rb2, and Rc, limited herb-drug interaction between valsartan and ginsenoside Rb1, Rb2, and Rc would be expected in human. In case of co-administration of valsartan and rifampin, a significant drug interaction between valsartan and rifampin was found ( Figure 5A) because unbound concentration of rifampin (4.7-22.9 µM) would exceed the IC 50 values required for OATP inhibition considering the plasma concentration (over 5 µg/mL for 12 h and C max of 15.7-24.5 µg/mL) and protein binding of rifampin (23.1%) in rats following oral administration of rifampin 20 mg/kg [23,39,40].…”

Amphiphilic block copolymers-based mixed micelles for noninvasive drug delivery

“…Moreover, most of the copolymers exhibited excellent biocompatibility and biodegradability. For instance, Pluronic copolymers could inhibit drug-efflux of P-glycoprotein (P-gp) and metabolism of cytochrome P450, and bile salts showed strong solubilizing capacity, and poly(ethylene glycol; PEG) copolymers acted as a eminent stabilizer avoided the recognition of the reticuloendothelial system (Ma et al, 2011;Tan et al, 2013;Zhang et al, 2014b). In addition, nano-sized MMs in range of 20-200 nm are enough large to avoid rapid elimination by glomerular filtration, and also small sufficiently to across blood vessels and facilitate passive targets to lower nonspecific organ toxicities (Li & Huang, 2008;Attia et al, 2011).…”