Comparative pharmacokinetics of two intravenous administration regimens of tiludronate in healthy adult horses and effects on the bone resorption marker CTX-1.
Bioavailability and pharmacological effects of tiludronate were compared when administered as an intravenous (i.v.) bolus at a dosage of 0.1 mg/kg body weight (b.w.) once daily for 10 consecutive days (group 1, n = 6) and as a single constant rate infusion (CRI) at a total dose of 1 mg/kg b.w. (group 2, n = 6) in healthy adult horses. Tiludronate and carboxy-terminal cross-linking telopeptide of type I collagen (CTX-1) were measured in plasma and urine. There was no statistically significant difference in area under the curve (AUC) and clearance (Cl) between the two groups. Bioavailability of the CRI was 103% (not significantly different) that of the 10 daily i.v. bolus doses. Cumulative urine tiludronate excretion could not be compared between groups because of poor sensitivity of the assay in urine. Plasma and urine CTX-1 levels were not different between groups throughout the study. However, interindividual variations were greater in group 1 than in group 2. A significant decrease in CTX-1 levels was observed in plasma after the first administration in group 1, but not in urine; while in group 2, a significant decrease in CTX-1 concentrations was observed after treatment in both plasma and urine. In conclusion, both dosage regimens of tiludronate produced similar plasma exposure and pharmacological effects in adult healthy horses.
Delguste
C
C
Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Liege, Liege, Belgium. cdelguste@ulg.ac.be
Amory
H
H
Guyonnet
J
J
Thibaud
D
D
Garnero
P
P
Detilleux
J
J
Lepage
O M
OM
Doucet
M
M
D000818:Animals; D019540:Area Under Curve; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D016723:Bone Remodeling / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical; D024042:Collagen Type I / Q000097:blood / Q000187:drug effects* / Q000652:urine; D004164:Diphosphonates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006736:Horses / Q000378:metabolism*; D007262:Infusions, Intravenous / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male
D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; C058651:tiludronic acid