Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Nov 3;21(21):8224.
doi: 10.3390/ijms21218224.

Pharmaceutical Excipients and Drug Metabolism: A Mini-Review

Rahul Patel  1 , James Barker  1 , Amr ElShaer  1
Affiliations
Review

Pharmaceutical Excipients and Drug Metabolism: A Mini-Review

Rahul Patel et al. Int J Mol Sci. .

Abstract

Conclusions from previously reported articles have revealed that many commonly used pharmaceutical excipients, known to be pharmacologically inert, show effects on drug transporters and/or metabolic enzymes. Thus, the pharmacokinetics (absorption, distribution, metabolism and elimination) of active pharmaceutical ingredients are possibly altered because of their transport and metabolism modulation from the incorporated excipients. The aim of this review is to present studies on the interaction of various commonly-used excipients on pre-systemic metabolism by CYP450 enzymes. Excipients such as surfactants, polymers, fatty acids and solvents are discussed. Based on all the reported outcomes, the most potent inhibitors were found to be surfactants and the least effective were organic solvents. However, there are many factors that can influence the inhibition of CYP450, for instance type of excipient, concentration of excipient, type of CYP450 isoenzyme, incubation condition, etc. Such evidence will be very useful in dosage form design, so that the right formulation can be designed to maximize drug bioavailability, especially for poorly bioavailable drugs.

Keywords: Pharmaceutical excipients; cytochrome P450; metabolism.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram depicting the route of poor bioavailability after oral administration of the drugs.
Figure 2
Figure 2
Illustrates the inhibition of CYP2C, CYP2D, CYP2E, CYP3A and CYP1A by acetonitrile, methanol, ethanol, acetone and DMSO at 1% and 10% concentrations.
Figure 3
Figure 3
Roadmap of various reported organic solvents based on their inhibitory effect on CYP450 system. The size of each circle represents the potency of various organic solvents and the lines depict the order of inhibition: from DMSO being the most potent to N,N-dimethylformamide being the least.
See this image and copyright information in PMC

References

    1. Sastry S.V., Nyshadham J.R., Fix J.A. Recent technological advances in oral drug delivery—A review. Pharm. Sci. Technol. Today. 2000;3:138–145. doi: 10.1016/S1461-5347(00)00247-9. - DOI - PubMed
    1. Major Advances in Oral Drug Delivery over the Past 15 Years. [(accessed on 24 July 2020)]; Available online: https://www.americanpharmaceuticalreview.com/Featured-Articles/148747-Ma...
    1. Zhang W., Li Y., Zou P., Wu M., Zhang Z., Zhang T. The Effects of Pharmaceutical Excipients on Gastrointestinal Tract Metabolic Enzymes and Transporters—An Update. AAPS PharmSciTech. 2016;18:830–843. doi: 10.1208/s12248-016-9928-8. - DOI - PubMed
    1. Pathak K., Raghuvanshi S. Oral Bioavailability: Issues and Solutions via Nanoformulations. Clin. Pharmacokinet. 2015;54:325–357. doi: 10.1007/s40262-015-0242-x. - DOI - PubMed
    1. Ezra A., Golomb G. Administration routes and delivery systems of bisphosphonates for the treatment of bone resorption. Adv. Drug Deliv. Rev. 2000;42:175–195. doi: 10.1016/S0169-409X(00)00061-2. - DOI - PubMed

MeSH terms

Substances