{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T15:03:13Z","timestamp":1751641393682},"reference-count":11,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\nBackground 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.<\/jats:p><jats:p>\nObjectives This analysis aimed to evaluate the profiles of parathyroid hormone (PTH) and calcium (Ca) concentrations in Taiwanese SHPT patients on hemodialysis and maxacalcitol.<\/jats:p><jats:p>\nMethods 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.<\/jats:p><jats:p>\nResults 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.<\/jats:p><jats:p>\nConclusions 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.<\/jats:p>","DOI":"10.1055\/a-1581-7609","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T23:19:35Z","timestamp":1630970375000},"page":"23-33","source":"Crossref","is-referenced-by-count":1,"title":["Maxacalcitol Pharmacokinetic\u2013Pharmacodynamic Modeling and Simulation for Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis"],"prefix":"10.1055","volume":"72","author":[{"given":"Mizuki","family":"Fukazawa-Shinotsuka","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohisa","family":"Saito","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaichi","family":"Abe","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satofumi","family":"Iida","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I-Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Chugai Pharma Taiwan Ltd, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimio","family":"Terao","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsi-Hsien","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-Che","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Taipei Medical University Hospital, Taipei, Taiwan"},{"name":"School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"ref2","doi-asserted-by":"crossref","first-page":"e03538","DOI":"10.1016\/j.heliyon.2020.e03538","article-title":"Comparative pharmacokinetics of maxacalcitol in healthy Taiwanese and Japanese subjects","volume":"6","author":"M-C Liu","year":"2020","journal-title":"Heliyon"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.4009\/jsdt.32.1079","article-title":"Clinical efficacy of 22-oxacalcitriol against secondary hyperparathyroidism in hemodialysis patients","volume":"32","author":"K Miyataka","year":"1999","journal-title":"Nihon Toseki Igakkai Zasshi"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1023\/A:1012299115260","article-title":"Ways to fit a PK model with some data below the quantification limit","volume":"28","author":"S L Beal","year":"2001","journal-title":"J Pharmacokinet 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Beto","year":"2019","journal-title":"J Ren Nutr"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1007\/s10157-014-0949-2","article-title":"Evidence-based Clinical Practice Guideline for CKD 2013","volume":"18","author":"Japanese Society of N","year":"2014","journal-title":"Clinical and Experimental Nephrology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1046\/j.1440-1797.1998.d01-28.x","article-title":"In vitro suppression of parathyroid hormone secretion by 22-oxa-calcitriol in human parathyroid hyperplasia due to uraemia","volume":"4","author":"K Sato","year":"2008","journal-title":"Nephrology"}],"container-title":["Drug 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