Bisphosphonates hinder bone remodelling by inhibiting osteoclast activity. Zoledronic acid (ZA) is a nitrogenous bisphosphonate used to increase bone density in humans. Tildren®, (tiludronic acid (TA)) is a non-nitrogenous bisphosphonate registered to treat lameness with bone and cartilage changes in adult horses. It is contraindicated in horses younger than 2 years. Bisphosphonates could be used in racehorses to reduce bone-related training injuries with potentially diabolical consequences.
Four mares and four geldings (mean age: 8 ± 2 years; mean body weight: 593 ± 59 kg) were dosed at 0.057 mg/kg ZA via IV infusion at 20 mL/min over 30 mins. Blood samples were taken prior to infusion and 1 min after infusion completion, then at increasing intervals to 60 minutes, followed by 2-hour sampling to 12 hours, then daily from 24 hours to 168 hours. Weekly samples were taken to 28 days.
Ten months later the same horses were dosed at 1.0 mg/kg disodium tiludronate infused IV at 20 mL/min over 30 minutes. Blood was collected daily for 6 days before treatment, then at the same time points as the ZA administration.
Plasma was analysed for ZA and TA using HPLC-MS/MS with pharmacokinetic parameters calculated by non-compartmental analysis using Phoenix WinNonLin.
Plasma ZA was highly variable between horses. Despite no statistical differences between sexes, plasma ZA was below the limit of detection (10 ng/mL) in all mares by 3 hours. Two geldings had detectable plasma ZA at 6 hours, with another gelding having detectable plasma ZA at 8 hours post-administration.
Plasma TA was statistically significantly higher in mares compared to geldings in the first 24 hours but not from 48 hours onwards. Despite substantial decreases over the first 24 hours, plasma TA was detected above the limit of quantification (1 ng/mL) in all horses 28 days after TA infusion.