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Population Pharmacokinetics and Detection Times of Betamethasone After Intravenous, Intramuscular, and Intranasal Jet Administration of Betamethasone Sodium Phosphate in Horses.
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.
© 2026 The Author(s). Drug Testing and Analysis published by John Wiley & Sons Ltd.
Publication Date: 2026-09-03 PubMed ID: 42693754DOI: 10.1002/dta.70144Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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Overview
- This study investigated how betamethasone sodium phosphate (BETP), a corticosteroid, is processed and cleared from horses’ bodies when administered intravenously, intramuscularly, or via an intranasal jet.
- It aimed to determine plasma and urine concentration thresholds and estimate detection times for medication control, which are critical for regulating its use in equine sports.
Background and Purpose
- Betamethasone sodium phosphate (BETP) is commonly used as an anti-inflammatory glucocorticoid in humans and can also be used off-label in horses.
- Understanding BETP’s pharmacokinetics—how it is absorbed, distributed, metabolized, and eliminated—is essential for detecting its presence in horse plasma and urine and for proper medication regulation.
- The study focused on three administration routes: intravenous (IV), intramuscular (IM), and intranasal jet (INJ), since different routes may affect drug absorption and elimination times.
- The primary goal was to derive “irrelevant plasma concentrations” (IPC) and “irrelevant urine concentrations” (IUC), which are low concentration thresholds meant to help regulators distinguish between therapeutic drug use and doping.
- The secondary goal was to estimate detection times (DTs)—the period after dosing during which betamethasone remains detectable above internationally recognized screening limits (ISL) in plasma and urine.
Methods
- Subjects: 20 horses from Japan and Germany; some horses received more than one administration route.
- Dosing regimens:
- IV administration: Single doses of 0.06 mg/kg (n=7) and 0.04 mg/kg (n=8).
- IM administration: Single dose of 20 mg per horse (n=7).
- INJ administration: Multiple doses of 4 mg per horse daily for 5 days (n=6).
- Sampling: Plasma and urine samples were collected post-administration to measure betamethasone concentrations over time.
- Data Analysis: A nonlinear mixed-effects pharmacokinetic model was used to estimate drug clearance and compartmental distribution parameters.
- Estimates:
- Plasma clearance rate (the volume of plasma cleared of the drug per kilogram of body weight per hour).
- Steady-state urine-to-plasma concentration ratio to relate urine measurements to plasma levels.
- IPC and IUC values based on estimated systemic clearance and dosing schedules.
- Detection times based on when drug concentrations fall below the International Federation of Horseracing Authorities (IFHA) ISL of 0.2 ng/mL in urine.
Key Results
- Plasma clearance was calculated to be 276 mL/kg/h, indicating a relatively rapid elimination of BETP from plasma.
- The steady-state urine-to-plasma concentration ratio was high at 25.8, meaning urine concentrations are substantially higher than plasma concentrations for the same drug exposure.
- Irrelevant plasma concentrations (IPC) for daily IV administrations were:
- 0.018 ng/mL for 0.06 mg/kg
- 0.012 ng/mL for 0.04 mg/kg
- Corresponding irrelevant urine concentrations (IUC) were:
- 0.47 ng/mL (close to ISL of 0.2 ng/mL) for 0.06 mg/kg dosing
- 0.31 ng/mL for 0.04 mg/kg dosing
- Detection times relative to ISL:
- After single IV doses (both 0.06 and 0.04 mg/kg), all horses had urine concentrations below the ISL within 72 hours.
- Following single IM administration, horses similarly fell below the ISL within 72 hours.
- After multiple intranasal jet doses (4 mg daily for 5 days), the detection time shortened, with horses below ISL within 48 hours.
Interpretation and Implications
- The rapid clearance and relatively short detection times suggest that betamethasone sodium phosphate, when used at typical therapeutic doses, clears from horse plasma and urine within a few days.
- The high urine-to-plasma ratio confirms urine sampling is a sensitive method for detecting BETP presence.
- Detection times can guide regulatory bodies in enforcing medication withdrawal times before competitions to avoid positive doping tests.
- Use of human BETP products in horses must be closely regulated, considering differences in dosing and administration routes can influence detection windows.
- The study’s model-based IPC and IUC values can help define thresholds for regulatory screening and confirmatory testing in equine sports.
- However, the authors note that the applicability of detection times should be interpreted within the specific regulatory framework and jurisdictional rules governing BETP use.
Conclusions
- This pharmacokinetic study provides valuable data on betamethasone elimination in horses across three administration routes.
- The derived thresholds and detection times can assist horseracing authorities and veterinarians in managing BETP use and controlling medication to maintain fair competition and horse welfare.
- The findings underscore the importance of route-specific pharmacokinetics in understanding drug residues and optimizing doping control strategies.
Cite This Article
APA
Kuroda T, Machnik M, Thevis M, Minamijima Y, Leung GN, Nomura M, Mizobe F, Ishikawa Y, Kamiya K, Toutain PL.
(2026).
Population Pharmacokinetics and Detection Times of Betamethasone After Intravenous, Intramuscular, and Intranasal Jet Administration of Betamethasone Sodium Phosphate in Horses.
Drug Test Anal.
https://doi.org/10.1002/dta.70144 Publication
Researcher Affiliations
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
- Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Japan.
- Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.
- Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.
- Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Japan.
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
- Racehorse Hospital, Miho Training Center, Japan Racing Association, Inashiki, Japan.
- Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
- Equine Department Main Office, Japan Racing Association, Tokyo, Japan.
- Comparative Biomedical Sciences, The Royal Veterinary College, London, UK.
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