Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen

Yung Yi Cheng, Elise T. Tuzo, Jeffrey W. Dalley, Tung Hu Tsai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Tamoxifen, a widely prescribed medication in premenopausal women diagnosed with hormone-dependent breast cancer, is potentially co-prescribed with Hedyotis diffusa (H. diffusa), particularly in Taiwan. However, no related report has investigated the drug-herb interaction of H. diffusa on the pharmacokinetics of tamoxifen and its metabolites. In the present study, male Sprague-Dawley rats were administered different doses of H. diffusa extract for 5 consecutive days prior to the administration of tamoxifen (10 mg/kg). A validated ultra-liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) system was developed to monitor tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen, and endoxifen in rat plasma. Pharmacokinetic results demonstrated that the area under curves (AUCs) of tamoxifen and the relative bioavailability (%) of tamoxifen were dose-dependently decreased (31–68%) by pre-treatment with H. diffusa extract (3 g/kg and 6 g/kg). In addition, the conversion ratio of 4-hydroxytamoxifen was downregulated (0.5-fold change) and the N-desmethyltamoxifen conversion ratio was upregulated (2-fold change) by high-dose H. diffusa extract. As a result, the relative bioavailability and biotransformation changes affect the clinical efficacy of tamoxifen treatment. These preclinical findings reveal a hitherto unreported interaction between tamoxifen and H. diffusa extract that has implications for their therapeutic efficacy in treating breast cancer.

Original languageEnglish
Article number112466
JournalBiomedicine and Pharmacotherapy
StatePublished - Jan 2022


  • 4-hydroxytamoxifen
  • Endoxifen
  • Hedyotis diffusa
  • Herb-drug pharmacokinetic interaction
  • Tamoxifen


Dive into the research topics of 'Dose-dependent effects of Hedyotis diffusa extract on the pharmacokinetics of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen'. Together they form a unique fingerprint.

Cite this