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

• Ahn JE
• Jeon S
• Lee J
• Han S
• Yim DS

• KMID: 2285513
• DOI: http://doi.org/10.4196/kjpp.2014.18.3.217

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

MeSH Terms

Absorption
Calcium Carbonate
Calcium*
Parathyroid Hormone*
Plasma
Tablets
Water
Calcium
Calcium Carbonate
Parathyroid Hormone
Tablets
Water

Figure

• 

  Fig. 1 Schematic of the model. ka, first-order absorption rate constant for Ca; F, relative bioavailability; kin_ca, zero-order input rate for Ca2+; kout_ca, first-order output rate constant for Ca2+; kin_pth, zero-order input rate for PTH; kout_pth, first-order output rate constant for PTH. *Unobserved.

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  Fig. 2 Diagnostic plots for observed Ca2+. DV, observed Ca2+; PRED, model predicted values; IPRED, individual model predicted values; CWRES, conditional weighted residuals. Gray lines are loess smooth.

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  Fig. 3 Diagnostic plots for observed PTH. DV, observed Ca2+; PRED, model predicted values; IPRED, individual model predicted values; CWRES, conditional weighted residuals. Gray lines are loess smooth.

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  Fig. 4 Visual predictive check for Ca2+. Obs, observed data; Sim, simulated values.

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  Fig. 5 Visual predictive check for PTH. Obs, observed data; Sim, simulated values.

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