Fluoride pharmacokinetics in the ewe: a linear pharmacokinetics model

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Veterinary Toxicology
• Animal Science

Background:

• Fluoride is a common environmental ion with potential toxicological implications in livestock.
• Understanding fluoride pharmacokinetics is crucial for assessing exposure risks and developing safety guidelines in sheep.
• Accurate kinetic data informs toxicity studies and risk assessment protocols.

Purpose of the Study:

• To investigate the pharmacokinetic profile of sodium fluoride in adult ewes.
• To determine if fluoride exhibits dose-dependent kinetics within a specific dosage range.
• To establish the suitability of intravascular fluoride administration for oral bioavailability assessments in sheep.

Main Methods:

• Administered sodium fluoride to 3 adult ewes at three dose levels (0.15, 0.375, 0.75 mg/kg bw).
• Analyzed pharmacokinetic data using both compartmental and noncompartmental modeling approaches.
• Utilized a 3-compartment open model to characterize fluoride distribution and elimination.

Main Results:

• Fluoride kinetics demonstrated linearity across the studied dose levels, indicating predictable behavior.
• Key pharmacokinetic parameters included an elimination half-life of 2.57 ± 1.28 h.
• Steady-state volume of distribution was 0.26 ± 0.5 L/kg, and body clearance was 0.105 ± 0.26 L/kg/h.

Conclusions:

• Fluoride exhibits linear pharmacokinetics in sheep at the tested doses.
• A single intravenous (bolus) administration of fluoride can be reliably used.
• This method is suitable for evaluating oral fluoride bioavailability in sheep toxicity studies.