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

Plasma ionized calcium ($Ca^{2+}$) 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 $Ca^{2+}$ 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 $Ca^{2+}$ and PTH data, respectively, in a manner that absorbed but unobserved $Ca^{2+}$ inhibits the secretion of PTH. Without notable changes in $Ca^{2+}$ levels, PTH responses were modeled and used as a marker for the extent of calcium absorption.