Tildren®, (tiludronic acid (TA)) is a non-nitrogenous bisphosphonate registered for the treatment of lameness with bone and cartilage changes in adult horses. It is contraindicated in horses younger than 2 years and the risk of abuse of Tildren® is real with potentially diabolical consequences. While several studies have retrospectively measured plasma TA in horses for drug detection, this study aimed to synchronise blood and urine samples to better understand TA metabolism and elimination by the horse.
Eight horses (four mares, four geldings; mean age: 9 ± 2 years; mean body weight: 591 ± 61 kg) had blood samples taken 6 days prior to and on the morning of drug administration. Horses were dosed at 1.0 mg/kg disodium tildronate infused IV at 20 mL/min over 30 minutes. Blood samples were taken 1 min after infusion completion, then at increasing intervals to 60 mins, followed by 2 h sampling to 12 h, then daily from 24 h to 168 h. Weekly samples were taken to 28 days. Plasma was analysed for TA using LCMS with pharmacokinetic parameters calculated by non-compartmental analysis using Phoenix WinNonLin.
Significant differences in plasma TA between geldings and mares occurred in the first 24 hours but not from 48 h onwards. There were substantial decreases in mean concentrations over the first 24 hours from 9752 ± 2427 ng/mL to 432 ± 163 ng/mL.
Plasma TA was detected above the limit of quantification (1 ng/mL) in all horses 28 days after TA infusion. There was a long elimination phase of the drug after initial rapid metabolism in the first 24 hours. Between 48 h and 28 days mean plasma concentrations decreased from 163 ± 60 ng/mL to 3 ± 1.3 ng/mL.