Drug interactions: Proteins, pumps, and P-450s.
The two major concerns in drug safety are adverse drug reactions and drug interactions. When multiple drug therapies are prescribed, drug interactions become an important consideration for patients and physicians. The life of a drug is reviewed with emphasis on absorption, distribution, metabolism, and excretion. Pharmacokinetic and pharmacodynamic mechanisms for drug interactions are reviewed. The contributions of P-glycoprotein, pharmacogenetic variation, and genetic polymorphisms to drug interactions are highlighted. Prediction of drug interactions is possible with knowledge of which agents are likely to cause alterations in drug metabolism. (J Am Acad Dermatol 2002;47:467-84.)


OBJECTIVE
At the conclusion of this learning activity, participants should have an understanding of the life of a drug. This knowledge should help predict important potential drug interactions.
Shapiro
Lori E
LE
Division of Clinical Pharmacology, Department of Medicine, Sunnybrook and Women's College Health Science Centre and the University of Toronto, Ontario, Canada.
Shear
Neil H
NH
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D001711:Biotransformation; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D029001:Herbal Medicine; D006801:Humans; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D013379:Substrate Specificity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D065607:Cytochrome P-450 Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A