エンザルタミドとカルシウム拮抗薬の薬物相互作用が血圧変動に及ぼす影響

抄録

Enzalutamide, a potent androgen-receptor inhibitor, is known to induce drug-metabolizing enzymes including cytochrome P450 (CYP) 3A4, 2C9, and 2C19. The antihypertensive effects of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB), which are substrates of CYPs, may be attenuated due to the CYP-inducing effects of enzalutamide. To examine the effect of enzalutamide on the antihypertensive role of CCBs and ARBs, we performed a retrospective investigation evaluating blood pressure in enzalutamide-treated prostate cancer patients taking or not taking CCBs or ARBs. The change in systolic blood pressure was calculated at the start of enzalutamide (day 0) and 4 ± 1 weeks later (day 28). The effect of the covariates on the change in blood pressure was analyzed using linear regression analysis. Univariate linear regression analysis showed that taking CCB and ARB were associated with increased blood pressure, but multiple regression analysis that simultaneously incorporated age, BMI, and dose of enzalutamide showed that only CCB was significantly associated. An interaction effect between CCB and dose of enzalutamide on systolic blood pressure change was also observed. A dose-dependent increase in blood pressure was observed with enzalutamide in the patients taking CCB. These results indicate that enzalutamide may cause a marked increase in blood pressure in patients being treated with CCB due to the dose-dependent CYP3A4 induction effect leading to a decrease in blood levels of CCB by enzalutamide.