Human cytochromes and some newer antidepressants: kinetics, metabolism, and drug interactions.
The appearance of selective serotonin reuptake inhibitor antidepressants in the mid-1980s caused the discipline of clinical psychopharmacology to refocus attention to the topics of drug metabolism and drug interactions. This article reviews the metabolic profiles of some newer antidepressants, the clinical implications of metabolic properties, and research methodology that can be applied in determining which specific human cytochromes P450 (CYP) mediate metabolic pathways. Also reviewed are the relative activities of various new antidepressants as inhibitors of CYPs, and the benefits and drawbacks of in vivo and in vitro methodologies for identification and quantitation of drug interactions.
Greenblatt
D J
DJ
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and New England Medical Center, Boston, Massachusetts 02111, USA. Dgreenblatt@Infonet.tufts.edu
von Moltke
L L
LL
Harmatz
J S
JS
Shader
R I
RI
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000493:pharmacokinetics*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D004347:Drug Interactions; D006801:Humans; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*
D018687:Antidepressive Agents, Second-Generation; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D017367:Selective Serotonin Reuptake Inhibitors