Comparative pharmacokinetics of two intravenous dosage rates of tiludronate in healthy adult horses

Plasma and urine pharmacokinetics of tiludronate administered once daily as an intravenous bolus of 0.1 mg/kg for ten consecutive days (group 1, n=6) was compared to a single slow infusion of 1 mg/kg (group 2, n=6) in healthy adult horses. Plasma samples were collected at regular intervals for a period of 16 and 7 days in groups 1 and 2 respectively. Continuous urine collection for determination of cumulative urinary excretion of tiludronate was performed during 16 and 7 days in groups 1 and 2 respectively, and over 24-hour periods every 10 days until 60 days after the last tiludronate administration in both groups. Tiludronate concentrations were obtained in all plasma and urine samples using HPLC with UV detection.
Plasma pharmacokinetic parameters were determined using a noncompartmental approach. Group 1 mean (± SD) AUCss was 3.76 (±0.698) mg.h.L-1 and group 2 mean (± SD) AUCtot was 39.07 (±3.699) mg.h.L-1. Mean (± SD) clearance (Cl) was 0.027 (±0.0042) and 0.026 (±0.0022) L.h-1.kg-1 in groups 1 and 2, respectively. Neither the dose corrected AUC (p=0.724) nor the Cl (p=0.528) were statistically different between groups. Relative plasma bioavailability (infusion versus bolus) was 103%.
Cumulative urine tiludronic acid excretion could not be compared between groups due to analytical limitations (LOQ of 0.025 mg.L-1), which led to numerous missing data particularly in group 1, and an inability to conduct appropriate statistical and pharmacokinetic analyses.
In conclusion, both dosage rates of tiludronate were considered bioequivalent with regards to plasma pharmacokinetics.