[en] Ibandronate, a potent, nitrogen-containing bisphosphonate for the treatment of postmenopausal osteoporosis, is the subject of an ongoing clinical development program to explore novel oral and intravenous (i.v.) dosing regimens. As part of this program, an extensive modeling and simulation project was undertaken to develop and validate a pharmacologically realistic mathematical model for ibandronate in osteoporosis, the aim being to identify practical dosing regimens for clinical evaluation. A simplified kinetics of drug action or kinetic-pharmacodynamic (K-PD) model (developed from a 4-compartment pharmacokinetic-pharmacodynamic [PK-PD] model) accurately described the urinary excretion of the C-telopeptide of the alpha-chain of type I collagen (uCTX). The model was extended to consider the effects of supplemental calcium therapy and allow simultaneous fitting of i.v. and oral ibandronate data, and then externally validated. This model was used successfully in the selection of appropriate once-monthly doses for further clinical evaluation and recent clinical studies have confirmed the efficacy of the doses identified. Further development of the model may include investigating the effects of ibandronate on bone mineral density and fracture risk, which would further enhance its clinical utility and predictive value. Although modeling and simulation has been used to explore the efficacy of other bisphosphonates, the extensive program with ibandronate has produced a comprehensively validated model that is the first to be prospectively tested by evaluating novel dosing regimens.
Disciplines :
General & internal medicine
Author, co-author :
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Gieschke, R.
Language :
English
Title :
Clinical utility of a pharmacostatistical model for ibandronate in postmenopausal osteoporosis
Publication date :
October 2006
Journal title :
Current Drug Metabolism
ISSN :
1389-2002
Publisher :
Bentham Science Publ Ltd, Sharjah, United Arab Emirates
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
Kauffman, W.J. and Smarr, L.L. (1993) Supercomputing and the transformation of science. Scientific American Library, New York.
Johnson, S. (1998) Drug Inf. J., 32, 961-969.
Reigner, B.B.; Williams, P.E.; Patel, I.H.; Steimer, J.L.; Peck, C. and Van Brummelen, P. (1997) Clin. Pharmacokinet., 33, 142-152.
Gieschke, R. and Steimner, J.L. (2000) Eur. J. Drug Metab. Pharmacokinet., 25, 49-58.
Goggin, T.; Gieschke, R.; Pillai, G.; Fotteler, B.; Jordan, P. and Steimer, J.L. (2002) in Simulation for Designing Clinical Trials: a Pharmacokinetic-Pharmacodynamic Modelling Perspective (Kimko, H. and Duffull, S.B. Eds.), Marcel Dekker, New York.
Gieschke, R.; Reigner, B.G. and Steimer, J.L. (1997) Int. J. Clin. Pharmacol. Ther., 35, 469-474.
FDA guidelines for preclinical and clinical evaluation of agents used in the prevention or treatment of postmenopausal osteoporosis (1994) www.fda.gov.
Barrett, J.; Worth, E.; Bauss, F. and Epstein, S. (2004) J. Clin. Pharmacol., 44, 951-965.
Reginster, J.-Y.; Wilson, K.M.; Dumont, E.; Bonvoisin, B. and Barrett, J. (2005) J. Clin. Endocrinol. Metab., 90, 5018-5024.
Bauss, F.; Endele, R.; Besenfelder, E. and Hoelck, J.-P. (2002) Calcif. Tissue Int., 70, 289-290.
Khan, S.A.; Kanis, J.A.; Vasikaran, S.; Kline, W.F.; Matsuzewski, B.K.; McCloskey, E.V.; Beneton, M.N.C.; Gertz, B.J.; Scribersras, D.G.; Holland, S.D.; Orgee, J.; Coombes, G.M.; Rogers, S.R. and Porras, A.G. (1997) J. Bone Miner. Res., 12, 1700-1707.
Hernandez, C.J.; Beaupré, G.S.; Marcus, R. and Carter, D.R. (2002) J. Bone Miner. Res., 17, 1662-1666.
Cremers, S.C.; Eekhoff, M.E.; Den Hartigh, J.; Hamdy, N.A.; Vermeij, P. and Papapoulos, S.E. (2003) J. Bone Miner. Res., 18, 868-875.
Cremers, S.; Den Sparidans, R.H.J.; Hamdy, N.; Vermeij, P. and Papapoulos, S. (2002) Eur. J. Clin. Pharmacol., 57, 883-890.
Mitchell, D.Y.; Eusebio, R.A.; Sacco-Gibson, N.A.; Pallone, K.A.; Kelly, S.C.; Nesbitt, J.D.; Brezovic, C.P.; Thompson, G.A. and Powell, J.H. (2000) J. Clin. Pharmacol., 40, 258-265.
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.