Comparative Pharmacokinetics of Two Intravenous Administration Regimens of Tiludronate in Healthy Adult Horses and Effects on the Bone Resorption Marker Ctx-1
horses; bisphosphonates; bone metabolism; biomarkers; pharmacology
Abstract :
[en] 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.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Delguste, Catherine ; Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie
Amory, Hélène ; Université de Liège - ULiège > Département clinique des animaux de compagnie et des équidés > Médecine interne des équidés
Guyonnet, J.
Thibaud, D.
Garnero, P.
Detilleux, Johann ; Université de Liège - ULiège > Département de productions animales > Génétique quantitative
Lepage, O. M.
Doucet, Michèle; Université de Montréal - UdeM > Biomédecine
Language :
English
Title :
Comparative Pharmacokinetics of Two Intravenous Administration Regimens of Tiludronate in Healthy Adult Horses and Effects on the Bone Resorption Marker Ctx-1
Publication date :
April 2008
Journal title :
Journal of Veterinary Pharmacology and Therapeutics
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