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

Publication ,  Journal Article
Kharasch, ED; Neiner, A; Kraus, K; Blood, J; Stevens, A; Miller, JP; Lenze, EJ
Published in: Clin Pharmacol Ther
November 2020

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, crossover study of brand and 3 generic bupropion XL 300 mg products measured steady-state enantiomeric plasma and urine parent bupropion and primary and secondary metabolite concentrations and evaluated bioequivalence and pharmacokinetics. Steady-state plasma and urine bupropion disposition was markedly stereoselective, with up to 40-fold differences in plasma concentrations of the active metabolite S,S-hydroxybupropion vs. R,R,-hydroxybupropion. Urine metabolite glucuronides were prominent, but glucuronidation was metabolite-specific and enantioselective. There were no differences between any generic and brand, or between generics, in plasma enantiomer concentrations of bupropion or the major metabolites. All generic products satisfied formal bioequivalence criteria (peak plasma concentration (Cmax ) and area under the plasma concentration-time curve over 24 hours (AUC0-24 )) using enantiomers for bupropion as well as for metabolites, and generics were comparable to each other, and were considered bioequivalent, based on enantiomeric analysis. Enantiomeric bioequivalence explains the previously observed therapeutic equivalence of bupropion generics and brand in treating major depression. These results have important implications for understanding the clinical therapeutic effects of bupropion based on complex and stereoselective metabolism.

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Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

November 2020

Volume

108

Issue

5

Start / End Page

1036 / 1048

Location

United States

Related Subject Headings

  • Therapeutic Equivalency
  • Stereoisomerism
  • Renal Elimination
  • Prospective Studies
  • Pharmacology & Pharmacy
  • Middle Aged
  • Male
  • Humans
  • Female
  • Drugs, Generic
 

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Chicago
ICMJE
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Kharasch, E. D., Neiner, A., Kraus, K., Blood, J., Stevens, A., Miller, J. P., & Lenze, E. J. (2020). Stereoselective Steady-State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults. Clin Pharmacol Ther, 108(5), 1036–1048. https://doi.org/10.1002/cpt.1888
Kharasch, Evan D., Alicia Neiner, Kristin Kraus, Jane Blood, Angela Stevens, J Philip Miller, and Eric J. Lenze. “Stereoselective Steady-State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults.Clin Pharmacol Ther 108, no. 5 (November 2020): 1036–48. https://doi.org/10.1002/cpt.1888.
Kharasch ED, Neiner A, Kraus K, Blood J, Stevens A, Miller JP, et al. Stereoselective Steady-State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults. Clin Pharmacol Ther. 2020 Nov;108(5):1036–48.
Kharasch, Evan D., et al. “Stereoselective Steady-State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults.Clin Pharmacol Ther, vol. 108, no. 5, Nov. 2020, pp. 1036–48. Pubmed, doi:10.1002/cpt.1888.
Kharasch ED, Neiner A, Kraus K, Blood J, Stevens A, Miller JP, Lenze EJ. Stereoselective Steady-State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults. Clin Pharmacol Ther. 2020 Nov;108(5):1036–1048.
Journal cover image

Published In

Clin Pharmacol Ther

DOI

EISSN

1532-6535

Publication Date

November 2020

Volume

108

Issue

5

Start / End Page

1036 / 1048

Location

United States

Related Subject Headings

  • Therapeutic Equivalency
  • Stereoisomerism
  • Renal Elimination
  • Prospective Studies
  • Pharmacology & Pharmacy
  • Middle Aged
  • Male
  • Humans
  • Female
  • Drugs, Generic