Comparative pharmacokinetics of maxacalcitol in healthy Taiwanese and Japanese subjects

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 ¼ 24) and healthy male Japanese subjects (n ¼ 24) were enrolled in separate singlecenter 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 C 5 and AUC inf appeared to increase with increase of doses in Taiwanese subjects (C 5 : 74.0, 159, and 321 pg/mL; AUC inf : 473, 763, and 1460 h･pg/mL) and Japanese subjects (C 5 : 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. C 5 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.

Maxacalcitol Pharmacokinetic–Pharmacodynamic Modeling and Simulation for Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis

“…The covariate effect of ethnicity on CL was 26.6 %, and the ratio (Taiwanese/Japanese) of estimated AUC was 1.36 based on the population mean. The estimated AUC was similar to the result from the actual clinical study that shows the geometric mean ratio (Taiwanese/Japanese) of AUC inf was 1.41 [2]. We considered intrinsic and extrinsic factors that might have had an influence on this ethnic difference.…”

“…If levels of intact parathyroid hormone (iPTH) in serum do not improve, the dose can be increased up to a maximum of 20 µg accompanied by close monitoring for the development of hypercalcemia. The pharmacokinetic (PK) profiles of maxacalcitol in healthy subjects and SHPT patients are similar, and maxacalcitol is metabolized by CYP3A4 and CYP24 in the liver rather than in the kidneys of patients with SHPT [2]. Maxacalcitol has a linear PK profile, and the half-life is approximately 5 h. Maxacalcitol is rapidly eliminated from serum, even in patients on hemodialysis [2].…”

“…The pharmacokinetic (PK) profiles of maxacalcitol in healthy subjects and SHPT patients are similar, and maxacalcitol is metabolized by CYP3A4 and CYP24 in the liver rather than in the kidneys of patients with SHPT [2]. Maxacalcitol has a linear PK profile, and the half-life is approximately 5 h. Maxacalcitol is rapidly eliminated from serum, even in patients on hemodialysis [2].…”

“…For the Taiwanese marketing approval, a clinical pharmacology study was conducted to compare PK and safety profiles between healthy Japanese and Taiwanese volunteers [2]. That study found the half-life of maxacalcitol in Taiwanese to be 1.5 -3.5 times the half-life in Japanese and that systemic maxacalcitol exposure was approximately 40 % higher in Taiwanese than in Japanese.…”

“…That study found the half-life of maxacalcitol in Taiwanese to be 1.5 -3.5 times the half-life in Japanese and that systemic maxacalcitol exposure was approximately 40 % higher in Taiwanese than in Japanese. Despite this difference in the PK of maxacalcitol between Japanese and Taiwanese [2], we hypothesized that the efficacy and safety profiles would not be affected by any factors such as a plateau in efficacy.…”