1. Pharmacokinetics of oral clonazepam in growing commercial pigs (Sus scrofa domestica).
- Author
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Hampton CE, Kleine SA, Smith JS, Mulon PY, Smith CK, Shanks GA, Vanecek LR, Seddighi R, and Cox S
- Subjects
- Animals, Swine, Administration, Oral, Male, Half-Life, Female, Hypnotics and Sedatives pharmacokinetics, Hypnotics and Sedatives administration & dosage, Hypnotics and Sedatives blood, Clonazepam pharmacokinetics, Clonazepam administration & dosage, Clonazepam blood, Area Under Curve
- Abstract
Clonazepam causes sedation and psychomotor impairment in people. Due to similarities between people and swine in response to benzodiazepines, clonazepam may represent a viable option to produce mild-to-moderate tranquillization in pigs. The objective of this study was to determine the pharmacokinetic profile of a single oral dose (0.5 mg/kg) of clonazepam in eight healthy, growing commercial cross pigs. Serial plasma samples were collected at baseline and up to 96 h after administration. Plasma concentrations were quantified using reverse-phase high-performance liquid chromatography, and compartment models were fit to time-concentration data. A one-compartment first-order model best fits the data. Maximum plasma concentration was 99.5 ng/mL, and time to maximum concentration was 3.4 h. Elimination half-life was 7.3 h, mean residence time 7.4 h, and apparent volume of distribution 5.7 L/kg. Achieved plasma concentrations exceeded those associated with psychomotor impairment in people although pharmacodynamic effects have not been investigated in pigs. A simulated oral regimen consisting of 0.35 mg/kg administered every 8 h to pigs would achieve plasma concentrations above 32 ng/mL which are shown to produce psychomotor impairment in people. Further studies to test the clinical efficacy of these dosages in commercial and miniature pigs are warranted., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
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