Comparative pharmacokinetics of maxacalcitol in healthy Taiwanese and Japanese subjects

Ming-Che Liu; Feng-Yi Chou; Yi-An Chien; Yen-Ju Chen; Masaichi Abe; Koki Furusho; Shunji Matsuki

doi:10.1016/j.heliyon.2020.e03538

Comparative pharmacokinetics of maxacalcitol in healthy Taiwanese and Japanese subjects

Heliyon. 2020 Mar 10;6(3):e03538. doi: 10.1016/j.heliyon.2020.e03538. eCollection 2020 Mar.

Authors

Ming-Che Liu¹, Feng-Yi Chou¹, Yi-An Chien², Yen-Ju Chen², Masaichi Abe³, Koki Furusho⁴, Shunji Matsuki⁴

Affiliations

¹ Clinical Research Center, Taipei Medical University Hospital, Taiwan.
² Chugai Pharma Taiwan Ltd., Taiwan.
³ Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
⁴ SOUSEIKAI Sugioka Memorial Hospital, Clinical Research Center (current SOUSEIKAI Fukuoka Mirai Hospital Clinical Research Center), Japan.

Abstract

Pharmacokinetic studies of maxacalcitol in healthy Taiwanese subjects have been conducted. This study to compare the pharmacokinetic properties of maxacalcitol in healthy Taiwanese and Japanese subjects. Healthy male Taiwanese subjects (n = 24) and healthy male Japanese subjects (n = 24) were enrolled in separate single-center and received a single intravenous dose of 1.25, 2.5 and 5 μg maxacalcitol. Male subjects were exclusively employed in the study due to the first administration of maxacalcitol to Taiwanese. Serum samples were collected for up to 72 h for pharmacokinetic analysis, and safety was assessed. Exposures to maxacalcitol as mean C₅ and AUC_inf appeared to increase with increase of doses in Taiwanese subjects (C₅: 74.0, 159, and 321 pg/mL; AUC_inf: 473, 763, and 1460 h･pg/mL) and Japanese subjects (C₅: 92.9, 174, and 346 pg/mL; AUC_inf: 312, 588, and 1040 h･pg/mL). After single bolus IV administration, linearity in maxacalcitol exposure was shown over the dose range of 1.25-5 μg in both Taiwanese and Japanese male healthy subjects. C₅ of maxacalcitol was slightly lower (85%) in Taiwanese compared with that in Japanese and AUC_inf of maxacalcitol in Taiwanese subjects was contrarily 15.0 (41.6%) higher than that in Japanese subjects, resulted in not much difference in pharmacokinetics of maxacalcitol between Taiwanese and Japanese. Moreover, maxacalcitol was well tolerated in both healthy Taiwanese and Japanese subjects.

Keywords: Direct comparison study; Maxacalcitol; Musculoskeletal system; Oxarol; Pharamcokinetics; Pharmaceutical science; Pharmacology; Phase I study; Physical chemistry; Renal system.