Effect of Cinacalcet Hydrochloride, a New Calcimimetic Agent, on the Pharmacokinetics of Dextromethorphan: In Vitro and Clinical Studies

• DOI: 10.1177/0091270007304103
• Publication Date: 2007-07-25T00:53:52Z
• Authors: Daisuke Nakashima; Hirotaka Takama; Yuko Ogasawara; Tetsuyoshi Kawakami; Tsuyoshi Nishitoba; Sakuo Hoshi; Eiji Uchida; Hideji Tanaka
• Keywords: Cinacalcet; Quinidine

Cinacalcet hydrochloride (cinacalcet) is a positive allosteric modulator of the calcium-sensing receptor indicated for treatment secondary hyperparathyroidism in dialysis patients. In vitro study has demonstrated that cinacalcet potent inhibitor cytochrome P450 (CYP) 2D6 with K(i) value 0.087 micromol/L, which comparable to well-known CYP2D6 inhibitor, quinidine (0.064 micromol/L). A clinical was conducted assess inhibitory effect on substrates healthy volunteers. Each subject received 50 mg or matched placebo orally once daily 8 days 30 dextromethorphan coadministered day 8. The mean AUC(0-infinity) and C(max) increased 11- 7-fold, respectively, extensive metabolizers when versus placebo. Therefore, during concomitant cinacalcet, it may be necessary consider making dose adjustments drugs narrow therapeutic index are mainly metabolized by CYP2D6.