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Irinotecan causes severe gastrointestinal damage, which may affect the expression of intestinal transporters. However, neither the expression of peptide transporter 1 (Pept1) nor the pharmacokinetics of Pept1 substrate drugs has been investigated under irinotecan‐induced gastrointestinal damage. Therefore, the present study quantitatively investigated the effects of irinotecan‐induced gastrointestinal damage on the intestinal expression of Pept1 and absorption of cephalexin (CEX), a typical Pept1 substrate, in rats. Irinotecan was administered intravenously to rats for 4 days to induce gastrointestinal damage. The expression of Pept1 mRNA and the Pept1 protein in the upper, middle, and lower segments of the small intestine of irinotecan‐treated rats was assessed by quantitative real‐time polymerase chain reaction (PCR) and western blotting, respectively. The pharmacokinetic profile of CEX was examined after its oral or intravenous administration (10 mg/kg). In irinotecan‐treated rats, ∼2‐fold increases in Pept1 protein levels were observed in all three segments, whereas mRNA levels remained unchanged. The oral bioavailability of CEX significantly decreased to 76% of that in control rats. The decrease in passive diffusion caused by intestinal damage may have overcome the increase in Pept1‐mediated uptake. In conclusion, irinotecan may decrease the intestinal absorption of Pept1 substrate drugs; however, it increased the expression of intestinal Pept1. [ABSTRACT FROM AUTHOR]

BACKGROUND: Capsaicin, as a major pungent ingredient of peppers, has many health benefits. However, the strong irritation effect of capsaicin inhibits its application in the food industry. Emulsions can be an effective approach to alleviate the irritation. RESULTS: In this study, we used tocopheryl polyethylene glycol 1000 succinate (TPGS) as an emulsifier to prepare capsaicin emulsions through high‐pressure homogenization. Capsaicin emulsions with a particle size of about 100 nm, −36.4 mV zeta potential, and 91.9% encapsulation efficiency were prepared successfully and showed better environmental stability and higher antioxidant activity. Emulsions reduced the cumulative release of capsaicin and had no toxic effect on buffalo rat liver (BRL‐3A) cells. Moreover, the gastrointestinal injury model of rats showed that emulsions reduced the strong irritation of capsaicin. CONCLUSION: This work provides a theoretical basis for the application of irritant ingredients in food industry. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Irinotecan causes serious gastrointestinal damage. Dabigatran etexilate (DABE), an oral anticoagulant and substrate of P‐glycoprotein (P‐gp), is poorly absorbed and exhibits low bioavailability in humans. The aim of this study was to evaluate the effects of irinotecan‐induced gastrointestinal damage on the pharmacokinetics/pharmacodynamics (PK/PD) of DABE. Irinotecan was administered intravenously to rats for 4 days to induce gastrointestinal damage. To investigate the PK profile of dabigatran (DAB), an active moiety of DABE, DABE was administered orally on day 5, and then DAB was administered intravenously on day 6. To evaluate the PD profile of DAB, the activated partial thromboplastin time (APTT) was measured. The protein expression level of intestinal P‐gp was evaluated. In the irinotecan‐treated rats, the area under the concentration–time curve of DAB after the oral administration of DABE and the bioavailability of DABE were decreased significantly. The APTT ratio also decreased, suggesting that the impaired efficacy of DABE was attributable to a reduction in its bioavailability. The expression of intestinal P‐gp was higher in the irinotecan‐treated rats. Taking into consideration the histological damage caused to the intestinal epithelium, both the increased P‐gp expression and the reduced passive diffusion were considered to be responsible for the reduction in the bioavailability of DABE. [ABSTRACT FROM AUTHOR]

Abstract: Preclinical Research & Development The objective of the present study was to evaluate the tapentadol–diclofenac combination in three dose‐ratios in the mouse acetic acid‐induced visceral pain and their ulcerogenic activity on the stomachal mucous. Dose‐response curves were generated for tapentadol, diclofenac, and their combination in the acetic acid‐induced writhing test in mice. Moreover, the stomachs of animals were surgically removal and gastrointestinal ulcerogenic action of the combination was assessed. The isobolographic analysis, interaction index, and ANOVA were used to analyze the data. The isobolographic analysis and interaction index showed a similar antinociceptive activity for the three combinations of the analgesic mixture. Moreover, tapentadol and the proportions 1:1 or 3:1 of the analgesic combination caused a mild gastrointestinal damage. These data indicate that the systemic co‐administration of tapentadol and diclofenac produced a synergistic interaction in the acetic acid‐induced visceral pain test with an acceptable gastric damage profile in mice. [ABSTRACT FROM AUTHOR]