Bupropion CYP2D6 metabolism

Bupropion is metabolized primarily by CYP2B6, and its metabolism may be altered by drugs such as cyclophosphamide, which is a substrate of 2B6. The major metabolite of bupropion, hydroxybupropion, is a moderate inhibitor of CYP2D6 and so can raise desipramine levels. Bupropion should be avoided in patients taking MAOIs. 

Bupropion is metabolized to hydroxybupropion primary by the cytochrome P450 CYP2B6 isoenzyme and to a much lesser extent by CYP1A2, -2A6, -2C9, -2E1, and -3A4. Bupropion and hydroxybupropion inhibit CYP2D6 in vitro. 

Drug-drug interactions The inhibitory effect of bupropion on CYP2D6 metabolism has been previously demonstrated in vivo, for example by inhibition of dextromethorphan metabolism (SEDA-30, 20). An in vitro study using desipramine as substrate has suggested that this effect is due to the metabolites erythrohydrobupropion and threohydrobupropion, which were much more potent inhibitors of CYP2D6 than hydroxybupropion or bupropion itself [71 ]. 

FLECAINIDE DRUG DEPENDENCE THERAPIES-BUPROPION t levels of flecainide Bupropion may inhibit CYP2D6-mediated metabolism of flecainide Monitor PR and BP closely start flecainide at the lowest dose for patients taking bupropion... 

AMPHETAMINES BUPROPION 1. t plasma concentrations of these substrates, with risk of toxic effects 2. t risk of seizures. This risk is marked in elderly people, patients with a history of seizures, those with an addiction to opiates/ cocaine/stimulants, and those with diabetes treated with oral hypoglycaemics or insulin 1. Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 2. Bupropion is associated with a dose-related risk of seizures. These drugs that lower seizure threshold are individually epileptogenic. They have additive effects when combined 1. Initiate therapy with these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. amphetamines) 2. Extreme caution. The dose of bupropion should not exceed 450 mg/day (or 150 mg/day in those with severe hepatic cirrhosis)... 

Bupropion inhibits the reuptake of both norepinephrine and dopamine it is used to assist smoking cessation. It is primarily metabolized by CYP2B6 isoenzymes and inhibits CYP2D6. 

ESCITALOPRAM, FLUOXETINE, FLUVOXAMINE, PAROXETINE, SERTRALINE BUPROPION T plasma concentrations of these SSRIs, with risk of toxic effects Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 Initiate therapy of these drugs at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. paroxetine)... 

Desipramine is metabolized by CYP2D6 and when co-administered with bupropion, its plasma half-life is prolonged by approximately... 

A study in 21 subjects who were quitting smoking and were CYP2D6 extensive metabolisers, found that 6 of 13 subjects who received bupropion 150 mg once daily for 3 days and then twice daily for 14 days had metabolic ratios of dextromethorphan 30 mg similar to those seen in poor metabolisers the metabolism of dextromethorphan to dextrorphan was substantially reduced. No such change was seen in the 8 subjects who received placebo. It has been suggested that care should be taken when ini-... 

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