Stereoselective Steady‐State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults

  title={Stereoselective Steady‐State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults},
  author={Evan D. Kharasch and Alicia Neiner and Kristin Kraus and Jane Blood and Angela Stevens and J. Philip Miller and Eric J. Lenze},
  journal={Clinical Pharmacology \& Therapeutics},
The antidepressant bupropion is stereoselectively metabolized and metabolite enantiomers have differential pharmacologic effects, but steady‐state enantiomeric disposition is unknown. Controversy persists about bupropion XL 300 mg generic equivalence to brand product, and whether generics might have different stereoselective disposition leading to enantiomeric non‐bioequivalence and, thus, clinical nonequivalence. This preplanned follow‐on analysis of a prospective, randomized, double‐blinded… 


Bioequivalence and Therapeutic Equivalence of Generic and Brand Bupropion in Adults With Major Depression: A Randomized Clinical Trial
Three bupropion XL 300 mg generic products are both bioequivalent and not therapeutically different from brand drug and each other, and three generics met formal bioequivalence criteria for buPropion and metabolites.
Chiral Plasma Pharmacokinetics and Urinary Excretion of Bupropion and Metabolites in Healthy Volunteers
The prediction of steady-state pharmacokinetics demonstrated differential stereospecific accumulation and elimination of bupropion effect and DDI risk with CYP2D6 at steady state, which may explain observed stereoselective differences.
Stereoselective Bupropion Hydroxylation as an In Vivo Phenotypic Probe for Cytochrome P4502B6 (CYP2B6) Activity
The clearance of racemic bupropion, metabolized selectively by CYP2B6 in vitro, has been used clinically to phenotype CYP2B6 activity, polymorphisms, and drug interactions but has known limitations.
Influence of CYP2B6 genetic variants on plasma and urine concentrations of bupropion and metabolites at steady state
As HB is active and its steady-state concentrations are more than 10 times higher than bupropion, CYP2B6 variants are likely to affect pharmacological activity.
Stereoselective Metabolism of Bupropion to OH-bupropion, Threohydrobupropion, Erythrohydrobupropion, and 4′-OH-bupropion in vitro
The stereoselective pharmacokinetics and the effect of drug-drug interactions (DDIs) and CYP2C19 pharmacogenetics on bupropion exposure were quantitatively explained by the in vitro metabolic clearances and in vivo interconversion between buPropion stereoisomers.
Common Polymorphisms of CYP2B6 Influence Stereoselective Bupropion Disposition
Clinical hydroxylation of both bupropion enantiomers was equivalently influenced by CYP2B6 allelic variation, which may affect therapeutic outcomes.
Stereoselective Glucuronidation of Bupropion Metabolites In Vitro and In Vivo
These data systematically describe the metabolic pathways underlying bupropion metabolite disposition and significantly expand the knowledge of potential contributors to the interindividual and intraindividual variability in therapeutic and toxic effects of buPropion in humans.
Stereoselective Metabolism of Bupropion by Cytochrome P4502B6 (CYP2B6) and Human Liver Microsomes
Stereoselective bupropion hydroxylation may have implications for the therapeutic efficacy of buPropion as an antidepressant or smoking cessation therapy, and for the use of bupropions as an in vivo phenotypic probe for CYP2B6 activity.
Identification of non‐reported bupropion metabolites in human plasma
Two non‐reported metabolites of bupropion are identified from human plasma in addition to the known hydroxybupropion, threo/erythrohydrob upropion and the glucuronidation products of the major metabolites (M2 and M4–M7).
Enantioselective Effects of Hydroxy Metabolites of Bupropion on Behavior and on Function of Monoamine Transporters and Nicotinic Receptors
The results suggest that clinical and behavioral effects of bupropion arise from actions at nAChR as well as DA and NE transporters and that the (2S,3S)-hydroxybupropion isomer may be a better drug candidate for smoking cessation because of its higher potency at the relevant targets.