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Open AccessArticle

Effect of Food and an Animal’s Sex on P-Glycoprotein Expression and Luminal Fluids in the Gastrointestinal Tract of Wistar Rats

1
UCL School of Pharmacy, University College London, 29–39 Brunswick Square, London WC1N 1AX, UK
2
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, China
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(4), 296; https://doi.org/10.3390/pharmaceutics12040296 (registering DOI)
Received: 26 February 2020 / Revised: 20 March 2020 / Accepted: 24 March 2020 / Published: 25 March 2020
The rat is one of the most commonly used animal models in pre-clinical studies. Limited information between the sexes and the effect of food consumption on the gastrointestinal (GI) physiology, however, is acknowledged or understood. This study aimed to investigate the potential sex differences and effect of food intake on the intestinal luminal fluid and the efflux membrane transporter P-glycoprotein (P-gp) along the intestinal tract of male and female Wistar rats. To characterise the intestinal luminal fluids, pH, surface tension, buffer capacity and osmolality were measured. Absolute P-gp expression along the intestinal tract was quantified via liquid chromatography-tandem mass spectrometry (LC-MS/MS). In general, the characteristics of the luminal fluids were similar in male and female rats along the GI tract. In fasted male rats, the absolute P-gp expression gradually increased from the duodenum to ileum but decreased in the colon. A significant sex difference (p < 0.05) was identified in the jejunum where P-gp expression in males was 83% higher than in females. Similarly, ileal P-gp expression in male rats was approximately 58% higher than that of their female counterparts. Conversely, following food intake, a significant sex difference (p < 0.05) in P-gp expression was found but in a contrasting trend. Fed female rats expressed much higher P-gp levels than male rats with an increase of 77% and 34% in the jejunum and ileum, respectively. A deeper understanding of the effects of sex and food intake on the absorption of P-gp substrates can lead to an improved translation from pre-clinical animal studies into human pharmacokinetic studies.
Keywords: P-glycoprotein; multidrug-resistant protein 1 (mdr1); ABCB1; preclinical development; sex differences; food effect; oral drug delivery; liquid chromatography tandem mass spectrometry (LC-MS/MS) P-glycoprotein; multidrug-resistant protein 1 (mdr1); ABCB1; preclinical development; sex differences; food effect; oral drug delivery; liquid chromatography tandem mass spectrometry (LC-MS/MS)
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MDPI and ACS Style

Dou, L.; Gavins, F.K.H.; Mai, Y.; Madla, C.M.; Taherali, F.; Orlu, M.; Murdan, S.; Basit, A.W. Effect of Food and an Animal’s Sex on P-Glycoprotein Expression and Luminal Fluids in the Gastrointestinal Tract of Wistar Rats. Pharmaceutics 2020, 12, 296.

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