Drug metabolism and drug transport of the 100 most prescribed oral drugs

Basic Clin Pharmacol Toxicol. 2022 Nov;131(5):311-324. doi: 10.1111/bcpt.13780. Epub 2022 Aug 24.


Safe and effective use of drugs requires an understanding of metabolism and transport. We identified the 100 most prescribed drugs in six countries and conducted a literature search on in vitro data to assess contribution of Phase I and II enzymes and drug transporters to metabolism and transport. Eighty-nine of the 100 drugs undergo drug metabolism or are known substrates for drug transporters. Phase I enzymes are involved in metabolism of 67 drugs, while Phase II enzymes mediate metabolism of 18 drugs. CYP3A4/5 is the most important Phase I enzyme involved in metabolism of 43 drugs followed by CYP2D6 (23 drugs), CYP2C9 (23 drugs), CYP2C19 (22 drugs), CYP1A2 (14 drugs) and CYP2C8 (11 drugs). More than half of the drugs (54 drugs) are known substrates for drug transporters. P-glycoprotein (P-gp) is known to be involved in transport of 30 drugs, while breast cancer resistance protein (BCRP) facilitates transport of 11 drugs. A considerable proportion of drugs are subject to a combination of Phase I metabolism, Phase II metabolism and/or drug transport. We conclude that the majority of the most frequently prescribed drugs depend on drug metabolism or drug transport. Thus, understanding variability of drug metabolism and transport remains a priority.

Keywords: ADME; CYP3A4; P-gp; drug metabolism; drug transport.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Cytochrome P-450 CYP1A2* / metabolism
  • Cytochrome P-450 CYP2C19 / metabolism
  • Cytochrome P-450 CYP2C8 / metabolism
  • Cytochrome P-450 CYP2C9 / metabolism
  • Cytochrome P-450 CYP2D6 / metabolism
  • Cytochrome P-450 CYP3A* / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Membrane Transport Proteins / metabolism
  • Microsomes, Liver
  • Neoplasm Proteins / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Membrane Transport Proteins
  • Neoplasm Proteins
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2C8
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A