Atypical antidepressants: Pharmacokinetics

Drug	Bioavailability (percent)	Time to peak plasma concentration (hours)	Primary metabolism*	Active metabolite(s)	Elimination half-life (hours)	Effect on drug metabolism (significant)*	Clearance
Agomelatine^¶	<5 Wide inter-individual variation; unaffected by food	1 to 2	CYP1A2 Avoid use with moderate or strong inhibitors of CYP1A2	No	1 to 2	None	Hepatic; avoid use in setting of hepatic impairment or active liver disease
Bupropion	Not available; modestly increased by food	Immediate release: 2 Sustained release: 3 Extended release: 5	CYP2B6 UGT glucuronidation	Yes (hydroxybupropion and others)	14 (parent, immediate release) 20 (parent, extended release) 21-51 (active metabolites)	Inhibits CYP2D6 (strong)	Hepatic and renal; dose adjustment may be needed in setting of renal or hepatic insufficiency
Mirtazapine	50 Unaffected by food	2	CYP1A2 CYP2D6 CYP3A4	Yes (N-desmethyl mirtazapine)	20 to 40 (parent) 25 (active metabolite) T ½ and serum concentrations are increased in female and older subjects	None	Hepatic and renal; dose adjustment may be needed in setting of renal or hepatic insufficiency

These classifications are based upon US Food and Drug Administration (FDA) guidance.^[1,2] Other sources may use a different classification system resulting in some agents being classified differently.

CYP: cytochrome P450; UGT: uridine diphosphate glucuronosyltransferase.
* Drug interactions and management suggestions may be determined by use of Lexi-Interact, the drug interactions program included with UpToDate.
¶ Not available in the United States.

References:

US Food and Drug Administration. Clinical drug interaction studies — Cytochrome P450 enzyme- and transporter-mediated drug interactions guidance for industry, January 2020. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions (Accessed on June 5, 2020).
US Food & Drug Administration. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Available at: FDA.gov website.

Spina E, Trifirò G, Caraci F. Clinically significant drug interactions with newer antidepressants. CNS Drugs 2012; 26:39.
Jefferson JW, Pradko JF, Muir KT. Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations. Clin Ther 2005; 27:1685.
McAllister-Williams RH, Baldwin DS, Haddad PM, Bazire S. The use of antidepressants in clinical practice: focus on agomelatine. Hum Psychopharmacol 2010; 25:95.
Croom KF, Perry CM, Plosker GL. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs 2009; 23:427.

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