Linked Life Data

18056047

Source:http://linkedlifedata.com/resource/pubmed/id/18056047

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-12-6
pubmed:abstractText
While initial preclinical studies provide an important starting point for dose selection, they may not provide adequate information to identify the optimal dosage for an extended treatment regimen. Determining the best dose for use in an extended dosing regimen requires ongoing development, illustrated best with the bisphosphonate, ibandronate. As mandated for regulatory purposes, the daily oral regimen of ibandronate was proven effective in significantly reducing the rate of new vertebral fractures assessed prospectively, and nonvertebral fractures in a high-risk population, assessed retrospectively. Extended dosing regimens, namely monthly and quarterly intravenous formulations, were developed subsequently to improve the convenience and enhance persistence, while maintaining or increasing efficacy. The continuing and progressive evolution of data led to the understanding that extension of drug-free interval requires higher annual cumulative skeletal exposures (ACE), which were not simply numerical multipliers of the interval and daily dose. For ibandronate, this led to dose selection for the oral monthly 150 mg (ACE 10.8 mg) and intravenous quarterly 3 mg (ACE 12 mg) formulations that proved superior in increasing bone mineral density (BMD) compared with oral daily 2.5 mg (ACE 5.5 mg) ibandronate. Pooling data from clinical trials with high ACE regimens (monthly and quarterly) led to the evolution of statistical evidence for a reduction in clinical and nonvertebral fractures with ibandronate. The ibandronate story should serve as an important future paradigm for bisphosphonate development.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
1117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
273-82
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Progression of efficacy with ibandronate: a paradigm for the development of new bisphosphonates.
pubmed:affiliation
The Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Review