Drug Interactions

A study of the in vitro ability of saw palmetto to inhibit the metabolic activity of cytochromes P450 3A4, 2D6, and 2C9 was recently studied (32). These investigators found that saw palmetto had no effect on the metabolism of model substrates of cytochrome P450 3A4 and 2D6. However, saw palmetto was noted to be a potent inhibitor of cytochrome P450 2C9 activity in vitro.

Two recent in vivo studies have attempted to evaluate the effect of saw palmetto administration on cytochrome P450 metabolic activity in humans. Markowitz and colleagues (33) studied the ability of saw palmetto administration for fourteen days to inhibit the metabolism of dextromethorphan and alprazolam, probe substrates for cytochrome P450 2D6 and 3A4, respectively. This study in six male and six female healthy volunteers found no effect of chronic saw palmetto administration on the metabolism or elimination of either probe substrate and, thus, no effect on either cytochrome P450 2D6 or 3A4 activity. In a similar study, Gurley and colleagues (34) evaluated the effect of saw palmetto on cytochrome P450 1A2, 2D6, 2E1, and 3A4 activity in vivo. A group of 12 healthy volunteers were administered saw palmetto for 28 days and phenotyped for each of the previously listed enzyme activities before and after saw palmetto administration. No significant effect of saw palmetto on any of the phenotypic ratios was noted, suggesting that saw palmetto has no effect on in vivo cytochrome P450 1A2, 2D6, 2E1, or 3A4 activity. These results of Markowitz et al. (33) and Gurley et al. (34) confirm the in vitro results of Yale and Glurich (32) regarding these enzymes. However, no in vivo studies have been conducted to date to evaluate whether saw pal metto affects cytochrome P450 2C9 activity, as suggested by Yale and Glurich. This has particular clinical significance because warfarin and phenytoin (both agents with narrow therapeutic indices) are metabolized by P450 2C9. Thus, clinical studies to evaluate this potential interaction are needed.

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