Biomaterial Database

Opioid pharmacokinetic drug-drug interactions. 2011

Brian R Overholser, and David R Foster

Department of Pharmacy Practice, College of Pharmacy, Purdue University, 1001 West 10th St., Indianapolis, IN 46202, USA.

Pharmacokinetic drug-drug interactions (DDIs) involving opioid analgesics can be problematic. Opioids are widely used, have a narrow therapeutic index, and can be associated with severe toxicity. The purpose of this review is to describe pharmacokinetic DDIs associated with opioids frequently encountered in managed care settings (morphine, codeine, oxycodone, oxymorphone, hydrocodone, hydromorphone, fentanyl, tramadol, and methadone). An introduction to the pharmacokinetic basis of DDIs is provided, and potential DDIs associated with opioids are reviewed. Opioids metabolized by the drug metabolizing enzymes of the cytochrome P450 (CYP450) system (codeine, oxycodone, hydrocodone, fentanyl, tramadol, and methadone) are associated with numerous DDIs that can result in either a reduction in opioid effect or excess opioid effects. Conversely, opioids that are not metabolized by that system (morphine, oxymorphone, and hydromorphone) tend to be involved in fewer CYP450-associated pharmacokinetic DDIs.

UI	MeSH Term	Description	Entries
D008329	Managed Care Programs	Health insurance plans intended to reduce unnecessary health care costs through a variety of mechanisms, including: economic incentives for physicians and patients to select less costly forms of care; programs for reviewing the medical necessity of specific services; increased beneficiary cost sharing; controls on inpatient admissions and lengths of stay; the establishment of cost-sharing incentives for outpatient surgery; selective contracting with health care providers; and the intensive management of high-cost health care cases. The programs may be provided in a variety of settings, such as HEALTH MAINTENANCE ORGANIZATIONS and PREFERRED PROVIDER ORGANIZATIONS.	Case Management, Insurance,Insurance Case Management,Managed Health Care Insurance Plans,Managed Care,Care, Managed,Managed Care Program,Management, Insurance Case,Program, Managed Care,Programs, Managed Care
D010597	Pharmacogenetics	A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).	Pharmacogenomics
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004347	Drug Interactions	The action of a drug that may affect the activity, metabolism, or toxicity of another drug.	Drug Interaction,Interaction, Drug,Interactions, Drug
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000701	Analgesics, Opioid	Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.	Opioid,Opioid Analgesic,Opioid Analgesics,Opioids,Full Opioid Agonists,Opioid Full Agonists,Opioid Mixed Agonist-Antagonists,Opioid Partial Agonists,Partial Opioid Agonists,Agonist-Antagonists, Opioid Mixed,Agonists, Full Opioid,Agonists, Opioid Full,Agonists, Opioid Partial,Agonists, Partial Opioid,Analgesic, Opioid,Full Agonists, Opioid,Mixed Agonist-Antagonists, Opioid,Opioid Agonists, Full,Opioid Agonists, Partial,Opioid Mixed Agonist Antagonists,Partial Agonists, Opioid