Population Pharmacokinetics and Detection Times of Betamethasone After Intravenous, Intramuscular, and Intranasal Jet Administration of Betamethasone Sodium Phosphate in Horses.
TL;DR
The applicability of the estimated DTs should be interpreted according to the regulatory framework governing the use of human BETP formulations and their routes of administration in the relevant jurisdiction.
Abstract
Betamethasone sodium phosphate (BETP) is a glucocorticosteroid used in humans. The primary objective was to estimate irrelevant plasma (IPC) and urine (IUC) concentrations using a pharmacokinetic/pharmacodynamic approach based on systemic clearance estimated from intravenous (IV) pharmacokinetic data. As a secondary objective, detection times (DTs) following IV, intramuscular (IM), and intranasal jet (INJ) administration were estimated for medication control. Plasma and urine concentrations were obtained from a total of 20 horses in Japan and Germany, with some horses contributing to more than one route after single IV (0.06 mg/kg, n = 7; 0.04 mg/kg, n = 8), single IM (20 mg/horse, n = 7), and multiple INJ (4 mg/horse for 5 days, n = 6) administration. The data were analyzed using a nonlinear mixed-effects model. The plasma clearance was 276 mL/kg/h, and the steady-state urine-to-plasma ratio was 25.8. For IV administration at 0.06 and 0.04 mg/kg every 24 h, the IPCs were 0.018 and 0.012 ng/mL, and the corresponding IUCs were 0.47 and 0.31 ng/mL, with the latter IUC close to the current International Federation of Horseracing Authorities international screening limit (ISL) (0.2 ng/mL). All horses fell below the ISL within 72 h after single IV administration at 0.06 and 0.04 mg/kg and after single IM administration, whereas all horses fell below the ISL within 48 h after INJ administration. The applicability of the estimated DTs should be interpreted according to the regulatory framework governing the use of human BETP formulations and their routes of administration in the relevant jurisdiction.