Drug Res (Stuttg) 2022; 72(01): 23-33
DOI: 10.1055/a-1581-7609
Original Article

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

Mizuki Fukazawa-Shinotsuka
1   Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Tomohisa Saito
1   Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Masaichi Abe
1   Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Satofumi Iida
1   Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
I-Ting Wang
2   Chugai Pharma Taiwan Ltd, Taipei, Taiwan
Kimio Terao
1   Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
Hsi-Hsien Chen
3   Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
Ming-Che Liu
4   Clinical Research Center, Taipei Medical University Hospital, Taipei, Taiwan
5   School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
› Author Affiliations


Background Maxacalcitol was approved in Taiwan in 2018 as the first active vitamin D3 injection for secondary hyperparathyroidism (SHPT) in patients on maintenance hemodialysis. However, no data from any clinical study with maxacalcitol in Taiwanese patients is available.

Objectives This analysis aimed to evaluate the profiles of parathyroid hormone (PTH) and calcium (Ca) concentrations in Taiwanese SHPT patients on hemodialysis and maxacalcitol.

Methods We developed population pharmacokinetic (PK) and pharmacodynamic (PD) models using a modeling and simulation approach. The data for these analyses were obtained from two studies: a clinical pharmacology study in Japanese patients and an ethnic comparison study in healthy Japanese and -Taiwanese volunteers. We then conducted a simulation study with a PK-PD model comprising the PK and PD models developed here.

Results Serum maxacalcitol concentration profile was modeled using a two-compartment model that took into consideration the distribution of concentrations below the lower limit of quantification. An ethnic difference in clearance was included in the PK model as a covariate. A PD model that used a PTH/Ca feedback loop best described the observed data. There were no significant differences in Ca or PTH concentrations between Taiwanese and Japanese based on the simulation results from our PK-PD model, even though maxacalcitol exposure was approximately 40% higher in Taiwanese than in Japanese.

Conclusions On the basis of these population PK and PD analyses and the clinical study conducted in Japan, there is no clinically relevant difference between Taiwanese and Japanese in terms of serum Ca or PTH levels.

Publication History

Received: 22 April 2021

Accepted: 03 August 2021

Article published online:
06 September 2021

© 2021. Thieme. All rights reserved.

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