A Physiologically Based Pharmacokinetic Model for Fluoride Uptake by Bone

Hari V. Rao, Robert P. Beliles, Gary M. Whitford, Charles H. Turner

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A sex-specific, physiologically based pharmacokinetic (pbpk) model has been developed to describe the absorption, distribution, and elimination of fluorides in rats and humans. Growth curves generated by plotting mean body weights (kg) against age (weeks or years) are included in the simulation model to allow the integration of chronic fluoride exposure from birth to old age. The model incorporates age and body weight dependence of the physiological processes that control the uptake of fluoride by bone and the elimination of fluoride by the kidneys. Six compartments make up the model. These are lung, liver, kidney, bone, and slowly and rapidly perfused compartments. The model also includes two bone subcompartments: a small, flow-limited, rapidly exchangeable surface bone compartment and a bulk virtually nonexchangeable inner bone compartment. The inner bone compartment contains nearly all of the whole body content of fluoride, which, in the longer time frame, may be mobilized through the process of bone modeling and remodeling. The model has been validated by comparing the model predictions with experimental data gathered in rats and humans after drinking water and dietary ingestion of fluoride. This physiological model description of absorption, distribution, and elimination of fluoride from the body permits the analysis of the combined effect of ingesting and inhaling fluorides on the target organ, bone. Estimates of fluoride concentrations in bone are calculated and related to chronic fluoride toxicity. The model is thus useful for predicting some of the long-term metabolic features and tissue concentrations of fluoride that may be of value in understanding positive or negative effects of fluoride on human health. In addition, the pbpk model provides a basis for across-species extrapolation of the effective fluoride dose at the target tissue, bone, in the assessment of risk from different exposure conditions.

Original languageEnglish (US)
Pages (from-to)30-42
Number of pages13
JournalRegulatory Toxicology and Pharmacology
Volume22
Issue number1
DOIs
StatePublished - Jan 1 1995

Fingerprint

Pharmacokinetics
Fluorides
Bone
Bone and Bones
Rats
Body Weight
Physiological models
Tissue
Physiological Phenomena
Kidney
Bone Remodeling
Extrapolation
Drinking Water
Liver
Inhalation
Process control
Toxicity

ASJC Scopus subject areas

  • Toxicology

Cite this

A Physiologically Based Pharmacokinetic Model for Fluoride Uptake by Bone. / Rao, Hari V.; Beliles, Robert P.; Whitford, Gary M.; Turner, Charles H.

In: Regulatory Toxicology and Pharmacology, Vol. 22, No. 1, 01.01.1995, p. 30-42.

Research output: Contribution to journalArticle

Rao, Hari V. ; Beliles, Robert P. ; Whitford, Gary M. ; Turner, Charles H. / A Physiologically Based Pharmacokinetic Model for Fluoride Uptake by Bone. In: Regulatory Toxicology and Pharmacology. 1995 ; Vol. 22, No. 1. pp. 30-42.
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