Polysaccharide Peptide Extract From Coriolus versicolor Increased Tmax of Tamoxifen and Maintained Biochemical Serum Parameters, With No Change in the Metabolism of Tamoxifen in the Rat

Valentina Razmovski-Naumovski; Benjamin Kimble; Daunia Laurenti; Srinivas Nammi; Hisayoshi Norimoto; Kelvin Chan

doi:10.3389/fphar.2022.857864

Polysaccharide Peptide Extract From Coriolus versicolor Increased T_max of Tamoxifen and Maintained Biochemical Serum Parameters, With No Change in the Metabolism of Tamoxifen in the Rat

Front Pharmacol. 2022 Apr 1:13:857864. doi: 10.3389/fphar.2022.857864. eCollection 2022.

Authors

Valentina Razmovski-Naumovski^{1

2

3}, Benjamin Kimble¹, Daunia Laurenti^{1

4}, Srinivas Nammi^{1

2}, Hisayoshi Norimoto⁵, Kelvin Chan^{1

6}

Affiliations

¹ NICM Health Research Institute, Western Sydney University, Penrith, NSW, Australia.
² School of Science, Western Sydney University, Penrith, NSW, Australia.
³ South West Sydney Clinical Campuses, Discipline of Medicine, University of New South Wales Sydney, Sydney, NSW, Australia.
⁴ School of Medicine, Western Sydney University, Penrith, NSW, Australia.
⁵ R&D Centre of PuraPharm Corporation Ltd. and PuraPharm (Nanning) Pharmaceutical Co. Ltd., Hong Kong, Hong Kong SAR, China.
⁶ School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom.

Abstract

Background: Polysaccharide peptide (PSP) extract of Coriolus versicolor (L.) Quél. (1886) (Trametes; Polyporaceae) is increasingly used in cancer to support the immune system. However, its interaction with tamoxifen is unknown. Aim of the study: To investigate the effect of a PSP extract on the pharmacokinetics, biochemical parameters, and depletion of tamoxifen. Methods: The pharmacokinetic and biochemical parameters of tamoxifen (20 mg/mL oral single dose and repeated dosing for 12 days) was investigated in female Sprague Dawley rats with or without PSP (340 mg/kg orally for 7 days) (n = 5 per group). Tamoxifen (5 µM) depletion rate with PSP (10-100 μg/mL) was measured in female rat hepatic microsomes in vitro. Results: Compared to tamoxifen alone, the time to reach maximum concentration (T_max) significantly increased by 228% (4.15 ± 1.15 versus 13.6 ± 2.71 h) in the single tamoxifen dose with PSP and 93% (6 ± 2.17 versus 11.6 ± 0.4 h) in the repeated tamoxifen dosing with PSP (p < 0.05). No significant changes in the area-under-curve and maximum concentration were observed in the single dose and repeated tamoxifen dosing plus PSP compared to tamoxifen alone. Pharmacodynamically, the repeated tamoxifen dosing with PSP maintained 19 out of 23 hepatic, renal and cardiac biochemical serum parameters in rats compared to untreated rats (p > 0.05). PSP extract did not significantly alter in vitro intrinsic clearance of tamoxifen compared to tamoxifen control. Conclusion: With the increased use of PSP as an adjunct therapy, this study highlights the importance of clinician's knowledge of its interaction with tamoxifen to avoid compromising clinical actions and enhancing clinical therapy.

Keywords: cancer; drug interaction; pharmacokinetics; polysaccharide peptide; traditional Chinese medicine; yunzhi.