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
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Alexandersen, P., Peris, P., Guanabens, N., Byrjalsen, I., Alvarez, L., Solberg, H. & Cloos, P.A. (2005) Non‐isomerized C‐telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget’s disease of bone. Journal of Bone and Mineral Research, 20, 588–595.
Barrett, J., Worth, E., Bauss, F. & Epstein, S. (2004) Ibandronate: a clinical pharmacological and pharmacokinetic update. Journal of Clinical Pharmacology, 44, 951–965.
Bauss, F. & Russell, R.G. (2004) Ibandronate in osteoporosis: preclinical data and rationale for intermittent dosing. Osteoporosis International, 15, 423–433.
Billinghurst, R.C., Brama, P.A., Van Weeren, P.R., Knowlton, M.S. & McIlwraith, C.W. (2003) Significant exercise‐related changes in the serum levels of two biomarkers of collagen metabolism in young horses. Osteoarthritis and Cartilage, 11, 760–769.
Bobba, R.S., Beattie, K., Parkinson, B., Kumbhare, D. & Adachi, J.D. (2006) Tolerability of different dosing regimens of bisphosphonates for the treatment of osteoporosis and malignant bone disease. Drug Safety, 29, 1133–1152.
Camacho, P. & Kleerekoper, M. (2006) Biochemical markers of bone turnover. In Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 6th edn. Ed Favus, M.J., pp. 127–133. American Society for Bone and Mineral Research, Washington, DC.
Carstanjen, B., Hoyle, N.R., Gabriel, A., Hars, O., Sandersen, C., Amory, H. & Remy, B. (2004) Evaluation of plasma carboxy‐terminal cross‐linking telopeptide of type I collagen concentration in horses. American Journal of Veterinary Research, 65, 104–109.
Coudry, V., Thibaud, D., Riccio, B., Audigie, F., Didierlaurent, D. & Denoix, J.M. (2007) Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column. American Journal of Veterinary Research, 68, 329–337.
Cremers, S. & Garnero, P. (2006) Biochemical markers of bone turnover in the clinical development of drugs for osteoporosis and metastatic bone disease: potential uses and pitfalls. Drugs, 66, 2031–2058.
Cremers, S.C., Pillai, G. & Papapoulos, S.E. (2005) Pharmacokinetics/pharmacodynamics of bisphosphonates: use for optimisation of intermittent therapy for osteoporosis. Clinical Pharmacokinetics, 44, 551–570.
Davi, H., Tronquet, C., Caix, J., Simiand, J., Briot, C., Berger, Y. & Thiercelin, J.F. (1999) Disposition of tiludronate (Skelid) in animals. Xenobiotica, 29, 1017–1031.
David, P., Nguyen, H., Barbier, A. & Baron, R. (1996) The bisphosphonate tiludronate is a potent inhibitor of the osteoclast vacuolar H(+)‐ATPase. Journal of Bone and Mineral Research, 11, 1498–1507.
Delguste, C., Amory, H., Doucet, M., Piccot‐Crezollet, C., Thibaud, D., Garnero, P., Detilleux, J. & Lepage, O.M. (2007) Pharmacological effects of tiludronate in horses after long‐term immobilization. Bone, 41, 414–421.
Denoix, J.M., Thibaud, D. & Riccio, B. (2003) Tiludronate as a new therapeutic agent in the treatment of navicular disease: a double‐blind placebo‐controlled clinical trial. Equine Veterinary Journal, 35, 407–413.
Fleisch, H.A. (1997) Bisphosphonates: preclinical aspects and use in osteoporosis. Annals of Medicine, 29, 55–62.
Guay, D.R. (2006) Ibandronate, an experimental intravenous bisphosphonate for osteoporosis, bone metastases, and hypercalcemia of malignancy. Pharmacotherapy, 26, 655–673.
Hannon, R. & Eastell, R. (2000) Preanalytical variability of biochemical markers of bone turnover. Osteoporosis International, 11 (Suppl. 6), S30–S44.
Ilter, E., Karalok, H., Tufekci, E.C. & Batur, O. (2006) Efficacy and acceptability of risedronate 5 mg daily compared with 35 mg once weekly for the treatment of postmenopausal osteoporosis. Climacteric, 9, 129–134.
Kellerhouse, P.L., Brown, C., Newhall, K., Judd, K. & Thompson, D. (2000) Assessment of bone resorption marker assays in Thoroughbred horses. Journal of Bone and Mineral Research, 15, S526.
Lasseter, K.C., Porras, A.G., Denker, A., Santhanagopal, A. & Daifotis, A. (2005) Pharmacokinetic considerations in determining the terminal elimination half‐lives of bisphosphonates. Clinical Drug Investigation, 25, 107–114.
Lein, M., Wirth, M., Miller, K., Eickenberg, H.U., Weissbach, L., Schmidt, K., Haus, U., Stephan, C., Meissner, S., Loening, S.A. & Jung, K. (2007) Serial markers of bone turnover in men with metastatic prostate cancer treated with zoledronic acid for detection of bone metastases progression. European Urology, 52, 1381–1387.
Lepage, O.M., Carstanjen, B. & Uebelhart, D. (2001) Non‐invasive assessment of equine bone: an update. Veterinary Journal, 161, 10–22.
Murakami, H., Takahashi, N., Tanaka, S., Nakamura, I., Udagawa, N., Nakajo, S., Nakaya, K., Abe, M., Yuda, Y., Konno, F., Barbier, A. & Suda, T. (1997) Tiludronate inhibits protein tyrosine phosphatase activity in osteoclasts. Bone, 20, 399–404.
Nenonen, A., Cheng, S., Ivaska, K.K., Alatalo, S.L., Lehtimaki, T., Schmidt‐Gayk, H., Uusi‐Rasi, K., Heinonen, A., Kannus, P., Sievanen, H., Vuori, I., Vaananen, H.K. & Halleen, J.M. (2005) Serum TRACP 5b is a useful marker for monitoring alendronate treatment: comparison with other markers of bone turnover. Journal of Bone and Mineral Research, 20, 1804–1812.
Papapoulos, S.E. & Schimmer, R.C. (2007) Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate. Annals of the Rheumatic Diseases, 66, 853–858.
Peris, P., Alvarez, L., Monegal, A., Guanabens, N., Duran, M., Echevarria, M., Ros, I., Ballesta, A.M. & Munoz‐Gomez, J. (2002) Effect of surgical menopause and Paget’s disease of bone on the isomerization of type I collagen carboxyterminal telopeptide: evolution after antiresorptive therapy. Journal of Bone and Mineral Metabolism, 20, 116–120.
Peris, P., Alvarez, L., Vidal, S., Kasper, D., Leeming, D.J., Monegal, A., Angeles Martinez, M., Pons, F. & Guanabens, N. (2006) Biochemical response to bisphosphonate therapy in pagetic patients with skull involvement. Calcified Tissue International, 79, 22–26.
Ravn, P., Neugebauer, G. & Christiansen, C. (2002) Association between pharmacokinetics of oral ibandronate and clinical response in bone mass and bone turnover in women with postmenopausal osteoporosis. Bone, 30, 320–324.
Reginster, J.Y., Wilson, K.M., Dumont, E., Bonvoisin, B. & Barrett, J. (2005) Monthly oral ibandronate is well tolerated and efficacious in postmenopausal women: results from the monthly oral pilot study. Journal of Clinical Endocrinology and Metabolism, 90, 5018–5024.
Rowland, M. & Tozer, T.N. (1995) Clinical Pharmacokinetics. Concepts and applications, 3rd edn. Lippincott Williams & Wilkins, Philadelphia, PA.
Sato, M., Grasser, W., Endo, N., Akins, R., Simmons, H., Thompson, D.D., Golub, E. & Rodan, G.A. (1991) Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. Journal of Clinical Investigation, 88, 2095–2105.
Stashak, T.S. (1998) Examination for lameness. In Adam’s Lameness in Horses, 5th edn. Ed Stashak, T.S., pp. 113–183. Lippincott Williams & Wilkins, Philadelphia, PA.
Tanko, L.B., Mouritzen, U., Lehmann, H.J., Warming, L., Moelgaard, A., Christgau, S., Qvist, P., Baumann, M., Wieczorek, L., Hoyle, N. & Christiansen, C. (2003) Oral ibandronate: changes in markers of bone turnover during adequately dosed continuous and weekly therapy and during different suboptimally dosed treatment regimens. Bone, 32, 687–693.
Tasker, J.B. (1966) Fluid and electrolyte studies in the horse. II. An apparatus for the collection of total daily urine and feces from horses. The Cornell Veterinarian, 56, 77–84.
Toutain, P.L. & Koritz, G.D. (1997) Veterinary drug bioequivalence determination. Journal of Veterinary Pharmacology and Therapeutics, 20, 79–90.
Varela, A., Lepage, O.M., Doucet, M., Marcoux, M. & Garnero, P. (2002) Tiludronate chez le cheval: tolérance et effets à court terme sur le métabolisme osseux. Annales de Médecine Vétérinaire, 147, 123–130.
Yun, M.H., Woo, J.S. & Kwon, K.I. (2006) Bioequivalence and pharmacokinetics of 70 mg alendronate sodium tablets by measuring alendronate in plasma. Archives of Pharmacal Research, 29, 328–332.
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.
