In Vitro and In Vivo Evaluations of Cytochrome P450 1A2 Interactions with Duloxetine

• Published in: Clinical pharmacokinetics Vol. 47; no. 3; pp. 191 - 202
• Main Authors: Lobo, Evelyn D., Bergstrom, Richard F., Reddy, Shobha, Quinlan, Tonya, Chappell, Jill, Hong, Quan, Ring, Barbara, Knadler, Mary Pat
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2008; Adis international; Wolters Kluwer Health, Inc; Springer Nature B.V
• Subjects: Administration, Oral; Adult; Area Under Curve; Biological and medical sciences; Biological Availability; Cross-Over Studies; Cytochrome P-450 CYP1A2 - drug effects; Cytochrome P-450 CYP1A2 - metabolism; Drug Interactions; Duloxetine Hydrochloride; Female; Fluvoxamine - pharmacology; General pharmacology; Humans; Infusions, Intravenous; Internal Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Microsomes, Liver - metabolism; Middle Aged; Original Research Article; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacotherapy; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - pharmacokinetics; Serotonin Uptake Inhibitors - pharmacology; Sex Factors; Smoking; Theophylline - pharmacokinetics; Thiophenes - adverse effects; Thiophenes - pharmacokinetics; Thiophenes - pharmacology; Duloxetine; Human Liver Microsome; Fluvoxamine; Theophylline; CYP1A2 Activity; Human; Intravenous administration; Serotonin; Psychotropic; Interaction; Oral administration; Catecholamine; Reuptake inhibitor; Metabolism; In vitro; In vivo; Cytochrome P450 1A2; Neurotransmitter; Antidepressant agent; Norepinephrine; Drug interaction; Pharmacokinetics

Objective: To determine whether duloxetine is a substrate, inhibitor or inducer of cytochrome P450 (CYP) 1A2 enzyme, using in vitro and in vivo studies in humans. Methods: Human liver microsomes or cells with expressed CYP enzymes and specific CYP inhibitors were used to identify which CYP enzymes c...