Korean J Physiol Pharmacol.  2014 Jun;18(3):217-223. 10.4196/kjpp.2014.18.3.217.

Modeling of the Parathyroid Hormone Response after Calcium Intake in Healthy Subjects

Affiliations
  • 1College of Pharmacy, Kangwon National University, Chuncheon 200-701, Korea.
  • 2Department of Clinical Pharmacology and Therapeutics, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 137-701, Korea. yimds@catholic.ac.kr
  • 3Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.

Abstract

Plasma ionized calcium (Ca2+) concentrations are tightly regulated in the body and maintained within a narrow range; thus it is challenging to quantify calcium absorption under normal physiologic conditions. This study aimed to develop a mechanistic model for the parathyroid hormone (PTH) response after calcium intake and indirectly compare the difference in oral calcium absorption from PTH responses. PTH and Ca2+ concentrations were collected from 24 subjects from a clinical trial performed to evaluate the safety and calcium absorption of Geumjin Thermal Water in comparison with calcium carbonate tablets in healthy subjects. Indirect response models (NONMEM Ver. 7.2.0) were fitted to observed Ca2+ and PTH data, respectively, in a manner that absorbed but unobserved Ca2+ inhibits the secretion of PTH. Without notable changes in Ca2+ levels, PTH responses were modeled and used as a marker for the extent of calcium absorption.

Keyword

Calcium; Indirect response model; Nonlinear mixed effects modeling; Parathyroid hormone
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