Drug interactions with newer antidepressants: role of human cytochromes P450.
Selective serotonin reuptake inhibitors and related antidepressant compounds have the secondary pharmacologic property of inhibiting the activity of human cytochrome P450 enzymes responsible for the oxidative metabolism of many drugs. A number of clinically important pharmacokinetic drug interactions are a consequence of these cytochrome inhibiting effects. This review evaluates the clinical implications of the metabolic profiles of the newer antidepressants, the relative activities of various new antidepressants as inhibitors of human cytochrome P450, and the various in vivo and in vitro methodologies that can be used for identification and quantification of drug interactions.
Greenblatt
D J
DJ
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and New England Medical Center, Boston, Mass 02111, USA. Dgreenblatt@Infonet.tufts.edu
von Moltke
L L
LL
Harmatz
J S
JS
Shader
R I
RI
D000928:Antidepressive Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D006900:Hydroxylation / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology
D000928:Antidepressive Agents; D019389:Cytochrome P-450 CYP2D6; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D017367:Selective Serotonin Reuptake Inhibitors