Drug-Drug Interactions

From PubPK

Drug-drug interactions occur when two or more drugs react with each other. Drug-drug interactions can lead to changed systemic exposure, resulting in variations in drug response of the co-administered drugs. Possible mechanisms of drug-drug interactions which can change pharmacokinetic profiles include: (1) influencing gastrointestinal absorption, (2) changing plasma and/or tissue protein binding, (3) transporter-based drug-drug interactions (including hepatic or renal uptake and biliary or urinary secretion), and (4) metabolism-based drug-drug interactions (Ito et al. 1998). Pharmacodynamic interactions such as antagonism at the receptor may also increase or decrease the effects of a drug.

Contents 1 Metabolism-Based Drug-Drug Interactions 1.1 Reversible Inhibition 1.1.1 Competitive Inhibition 1.1.2 Noncompetitive Inhibition 1.1.3 Uncompetitive Inhibition 1.2 Mechanism-based Inhibition 1.3 Induction 2 Transporter-Based Drug-Drug Interactions 3 See Also 4 External Links 5 References

Metabolism-Based Drug-Drug Interactions

Many metabolic routes of elimination, including most of those occurring through the P450 family of enzymes, can be inhibited or induced by concomitant drug treatment.

Reversible Inhibition

Competitive Inhibition

to be updated

Noncompetitive Inhibition

to be updated

Uncompetitive Inhibition

to be updated

Mechanism-based Inhibition

to be updated

Induction

to be updated

Transporter-Based Drug-Drug Interactions

Transporter-based interactions have been increasingly documented. Examples of these include the inhibition or induction of transport proteins, such as P-glycoprotein (P-gp), organic anion transporter (OAT), organic anion transporting polypeptide (OATP), organic cation transporter (OCT), multidrug resistance-associated proteins (MRP), and breast cancer resistant protein (BCRP).

See Also

• Prediction of In Vivo Drug-Drug Interactions from In Vitro Data
• Prediction of Pharmacokinetics
• Drug Transporters

External Links

• Drug Interactions: Cytochrome P450 Drug Interaction Table Indiana University School of Medicine
• Drug Development and Drug Interactions FDA
  • Tables of Substrates, Inhibitors and Inducers
    • Chemical inhibitors for in vitro experiments
    • Preferred and acceptable chemical substrates for in vitro experiments
    • Chemical Inducers for In Vitro Experiments
    • Examples of in vivo substrate, inhibitor, and inducer for specific CYP enzymes for study (oral administration)
    • Classification of CYP3A inhibitors
    • Classification of inhibitors of other CYP enzymes
    • Examples of sensitive CYP3A substrates or CYP3A substrates with narrow therapeutic range
    • Examples sensitive CYP substrates or CYP substrates with narrow therapeutic range
    • Acceptable In Vitro P-gp Substrates
    • In Vitro P-gp Inhibitors
    • Major human transporters
  • Possible Model for Decision Making
    • CYP-Based Drug-Drug Interaction Studies
    • P-gp-Based Drug-Drug Interaction Studies
    • P-gp Inhibitor and Digoxin Interaction Studies
• HIV Drug Interactions

References

• Ito K, Iwatsubo T, Kanamitsu S, Ueda K, Suzuki H, and Sugiyama Y (1998) Prediction of pharmacokinetic alterations caused by drug-drug interactions: metabolic interaction in the liver Pharmacol Rev 50: 387–412.