Polysaccharide peptide (PSP) extract from Coriolus versicolor decreased Tmax of tamoxifen and maintained biochemical serum parameters, with no change in the metabolism of tamoxifen in the rat

Abstract Background: Natural products such as mushrooms are increasingly used as adjunct therapies in cancer to stimulate the immune system. However, little is known about their interaction with chemotherapy drugs. This study investigated whether a commercial polysaccharide peptide (PSP) extract of the mushroom Coriolus (C.) versicolor interacts with tamoxifen, a common chemotherapy drug used in breast cancer. Methods: The pharmacokinetic and biochemical parameters of tamoxifen in female Sprague-Dawley rats’ serum were determined after orally administering tamoxifen (20 mg/kg) at a single dose and repeated dosing with and without C. versicolor (340 mg/kg). Results: Although the area-under-curve and maximum concentration showed no significant differences in both the single dose and repeated dosing, time to reach maximum concentration (Tmax) increased by 228% and 93%, respectively, in the rats treated with C. versicolor (p<0.05). The repeated dosing of C. versicolor, when co-administered with repeated dosing of tamoxifen, maintained 19 out of 23 biochemical serum parameters in rats compared to control (p<0.05). Using hepatic female rat microsomes, an in vitro study showed that the extract (10 – 100 µg/mL) did not significantly alter the rate of tamoxifen depletion which is known to be mediated by cytochromes P450 (CYP450). Conclusions: These results indicate that C. versicolor may delay the intestinal absorption of tamoxifen and maintain biochemical serum parameters, without any change in tamoxifen’s metabolism. If clinical trials confirm this result, the timing of tamoxifen and C. versicolor administration would need to be considered to avoid potential drug interactions resulting from a delay in achieving the systemic level of the anti-cancer medication.