Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIRO9K4QS)
Drug Name			Pentobarbital		Drug Info		Bupropion		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anxiolytics/Sedatives/Hypnotics				Antidepressants
Structure

Mechanism of Pentobarbital-Bupropion Interaction (Severity Level: Moderate)
CYP450 enzyme induction Click to Show/Hide Mechanism Graph

Drug Name		Pentobarbital				Bupropion
Mechanism 1		CYP450 inducer				CYP450 substrate
Key Mechanism Factor 1
		Factor Name		Cytochrome P450				Structure Sequence
		Protein Family		Cytochrome P450 family
		Protein Function		A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:20702771, PubMed:19965576, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:2732228, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:21576599, PubMed:21490593). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:14559847, PubMed:12865317). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:2732228, PubMed:15373842, PubMed:15764715, PubMed:22773874). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:2732228, PubMed:15373842, PubMed:15764715). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981). Click to Show/Hide
Mechanism Description		Increased metabolism of Bupropion caused by Pentobarbital mediated induction of CYP450 enzyme
Antagonize the effect of antiepileptic agents Click to Show/Hide Mechanism Graph

Drug Name		Pentobarbital				Bupropion
Mechanism 2		Antiepileptic agent				Lower seizure threshold
Key Mechanism Factor 2
		Factor Name		Antiepileptic agents
		Factor Description		The beneficial effects of antiepileptic drugs may be reduced, leading to an increase in seizure frequency or duration.
Mechanism Description		Antagonize the effect of Pentobarbital when combined with Bupropion

Recommended Action
Management		Pharmacologic response to bupropion should be monitored more closely whenever a barbiturate is added to or withdrawn from therapy, and the bupropion dosage adjusted as necessary. Although barbiturates and other sedatives may be prescribed to treat agitation, anxiety, and insomnia associated with bupropion use, patients should be alerted to the possibility of an increased risk of seizures during excessive exposure to these drugs. Patients should not attempt to alter the dosages or discontinue the medications on their own without consulting with their physician. The use of bupropion is contraindicated in patients undergoing abrupt discontinuation of sedatives.

References
1	James WA, Lippmann S "Bupropion: overview and prescribing guidelines in depression." South Med J 84 (1991): 222-4. [PMID: 1899294]
2	Product Information. Wellbutrin (bupropion). Glaxo Wellcome, Research Triangle Park, NC.