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Effect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers

. 2010 Apr;40(4):275-81.

doi: 10.3109/00498250903509383.

H-P Lei  1 , X-Y Yu, H-T Xie, H-H Li, L Fan, L-L Dai, Y Chen, H-H Zhou

Affiliations

Affiliation

  • 1 Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • PMID: 20102294
  • DOI: 10.3109/00498250903509383

H-P Lei et al. Xenobiotica. 2010 Apr.

. 2010 Apr;40(4):275-81.

doi: 10.3109/00498250903509383.

Authors

H-P Lei  1 , X-Y Yu, H-T Xie, H-H Li, L Fan, L-L Dai, Y Chen, H-H Zhou

Affiliation

  • 1 Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • PMID: 20102294
  • DOI: 10.3109/00498250903509383

Abstract

The objective of this study was to investigate the effects of continuous St. John's wort administration on single-dose pharmacokinetics of bupropion, a substrate of cytochrome P450 (CYP) 2B6, in healthy Chinese volunteers. Eighteen unrelated healthy male subjects participated in this study. The single-dose pharmacokinetics of bupropion and hydroxybupropion were determined before (control) and after a long-term period of St. John's wort intake (325 mg, three times a day for 14 days). Plasma concentrations of bupropion and hydroxybupropion were determined before and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60 and 72 h after dosing. St. John's wort treatment decreased the area under the concentration versus time curve extrapolated to infinity of bupropion in healthy volunteers from 1.4 microg.h ml(-1) (95% confidence interval [CI] = 1.2-1.6 microg.h ml(-1)) after bupropion alone to 1.2 microg.h ml(-1) (95% CI = 1.1-1.3 microg.h ml(-1)) during St. John's wort treatment. St. John's wort treatment increased the oral clearance of bupropion from 108.3 l h(-1) (95% CI = 95. 4-123.0 l h(-1)) to 130.0 l h(-1) (95% CI = 118.4-142.7 l h(-1)). No change in the time to peak concentration (t(max)) and the blood elimination half-life (t(1/2)) of bupropion was observed between the control and St. John's wort-treated phases. However, the half-life of hydroxybupropion between two phases had a significant difference by a Student's t test after logarithmic transformation. St. John's wort treatment decreased the half-life of hydroxybupropion from 26.7 h (95% CI = 23.8-29.9 h) to 24.4 h (95% CI = 21.9-27.3 h). St. John's wort decreased, to a statistically significant extent, the plasma concentrations of bupropion, probably mainly by increasing the clearance of bupropion.

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Publication types

MeSH terms

Substances

enzymes and interactions? : DrugNerds

I've been taking SJW for many years consistently. It has helped very well to combat my mild/moderate depression. Apart from some initial slight photosensitivity and minor libido side effects there seem to be no major downsides.

After extensive research I decided not to stop SJW when I was put on Bupropion (an NDRI antidepressant, mainly metabolised by CYP2D6 and CYP2B6), because it seems they don't compete for the same enzymes and the MAO inhibition of SJW seems to be negligible. But I know enzymes and drug interactions are very complex and I might have missed something. So I'm curious for feedback from this community.
EDIT: My question: Does SJW decrease the efficacy of Bupropion or does it have any other detrimental interactions?

SJW inhibiting/inducing enzymes
I'm well aware why many psychiatrists are so set against the use of SJW. SJW inhibits or induces a few important enzymes, like CYP3A4 (which is used in the metabolism of many drugs) and CYP2C9. https://www.ncbi.nlm.nih.gov/pubmed/15100173

These enzymes are pivotal to process many drugs.
See:https://en.wikipedia.org/wiki/CYP3A4#CYP3A4_ligands
https://en.wikipedia.org/wiki/CYP2C9#CYP2C9_Ligands

Bupropion inhibiting/inducing enzymes
See https://en.wikipedia.org/wiki/Bupropion#Pharmacology.
Mainly CYP2D6 and CYP2B6. Some mentions are made of slight inhibition/induction of other P450 enzymes (also CYP3A4), but it seems the linked research references don't corroborate this.

Relevant research I've found

Wiki Bupropion
https://en. wikipedia.org/wiki/Bupropion#Pharmacology

Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content
https://onlinelibrary.wiley.com/doi/full/10.1111/jphp.12858

Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John’s wort: an [11C]-harmine PET study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201991/

Herb-medicine interactions: St John’s wort (Hypericum perforatum)
http://nes.scot.nhs.uk/media/344030/stjohnswort.pdf

Mechanism of Action of St John’s Wort in Depression What is Known?
https://drugs-forum.com/data/attachment-files/2013/02/150577_Mechanism_of_Action_of_St_Johns_-_VButterweck.pdf

The Psychopharmacology of Bupropion: An Illustrated Overview
https://psychopharmacologyinstitute.com/antidepressants/bupropion-psychopharmacology/

Sertraline and Its Metabolite Desmethylsertraline, but not Bupropion or Its Three Major Metabolites, Have High Affinity for P-Glycoprotein
https://www. ncbi.nlm.nih.gov/pmc/articles/PMC2666302/

15 Years of Clinical Experience With Bupropion HCl: From Bupropion to Bupropion SR to Bupropion XL
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1163271/

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