Influene of Pharmaceutical Excipients on the Membrane Transport of a P-glycoprotein Substrate in the Rat Small Intestine


Background and Objectives

Generic drugs are generally used worldwide because of affordability compared to brand-name drugs. One of the main differences between brand-name and generic drugs is pharmaceutical excipients. We previously reported the effects of pharmaceutical excipients on the membrane permeation of drugs via the paracellular and transcellular routes, which are passive transport routes. P-glycoprotein (P-gp) is a typical ATP-binding cassette transporter and is mostly responsible for drug–drug interactions involving transporters. In the present study, rhodamine 123 (Rho123) was selected as the P-gp substrate, and the effects of pharmaceutical excipients on its membrane transport in the rat jejunum and ileum were examined.


Twenty major pharmaceutical excipients widely used in the pharmaceutical industry were selected. The in vitro diffusion chamber method using the rat jejunum and ileum was employed to investigate the effects of pharmaceutical excipients on the membrane permeation of Rho123.


The results obtained showed that the membrane permeability of Rho123 significantly (P < 0.05) changed under certain dosage conditions of pharmaceutical excipients such as sodium carboxymethyl starch, pullulan, glyceryl monostearate and so on. Furthermore, the effects of pharmaceutical excipients were site specific in the small intestine.


The present results demonstrated that some pharmaceutical excipients altered the membrane permeability of Rho123 in the rat small intestine.

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The authors thank Mr. Yuki Aizawa and Mr. Daisuke Makie for their technical assistance.

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Corresponding author

Correspondence to Yusuke Takizawa.

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This study was supported, in part, by a Grant-in-Aid for Young Scientists (B) (25860127) from the Japan Society for the Promotion of Sciences (JSPS).

Conflict of interest

The authors declare no conflicts of interest.

Ethics Approval

All animal experiments were performed according to the guidelines of the Tokyo University of Pharmacy and Life Sciences. The study was approved by the Tokyo University of Pharmacy and Life Sciences Committee on the Care and Use of Laboratory Animals (approval number: P12-65 and P13-42).

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Takizawa, Y., Goto, N., Furuya, T. et al. Influene of Pharmaceutical Excipients on the Membrane Transport of a P-glycoprotein Substrate in the Rat Small Intestine. Eur J Drug Metab Pharmacokinet (2020).

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