Abstract:
BACKGROUND AND OBJECTIVE:Bisphosphonates are commonly used to treat and prevent osteoporosis. These compounds have unusual pharmacokinetic characteristics because they bind strongly to bone, and a portion becomes buried under newly formed bone. Once incorporated into bone tissue, the subsequent release during bone remodeling is probably the rate-limiting step in the terminal elimination of bisphosphonates. Because of this unique property of bisphosphonates, pharmacokinetic studies with insufficient lengths of follow-up might entirely miss the true terminal elimination phase. A terminal half-life (t((1/2)gamma)) of approximately 11 years, similar to that of calcium and other minerals in bone, was reported from an 18-month study of alendronic acid in postmenopausal women with osteoporosis. We are not aware of any other published reports in which the elimination of a bisphosphonate has been followed for more than a few weeks post-dose. The purpose of the present study was to reanalyse the alendronic acid data to examine the effect of truncating the length of follow-up on the calculated t((1/2)gamma). PATIENTS AND METHODS:Twenty-one postmenopausal women with osteoporosis (mean age 66 years) received intravenous alendronic acid 30mg over 4 consecutive days (7.5 mg/day), and urinary excretion of alendronic acid was monitored over the following 18-24 months. Terminal elimination half-life was originally calculated by log-linear regression of the percentage retained versus time curve between days 240 and 540 and substituting the slope of the regression line into the equation, t((1/2)gamma) = -log 2/slope. These data were reanalysed based on the period up to 30 days. RESULTS:Data were sufficient for analysis of pharmacokinetics in 11 patients. A mean t((1/2)gamma) of approximately 11 years was reported previously, based on analysis of data between days 240 and 540. Recalculating the 'terminal' half-life of alendronic acid using only data from the first 30 days resulted in an 'observed' half-life of only 11 days. CONCLUSION:This analysis illustrates the importance of sufficient length of follow-up to accurately characterise the true terminal elimination half-life of bisphosphonates. The relatively short (expressed in units of days rather than years) terminal elimination half-lives reported for some bisphosphonates based on only 30 days of follow-up or less are likely to substantially underestimate the true terminal elimination half-lives.
journal_name
Clin Drug Investigjournal_title
Clinical drug investigationauthors
Lasseter KC,Porras AG,Denker A,Santhanagopal A,Daifotis Adoi
10.2165/00044011-200525020-00003subject
Has Abstractpub_date
2005-01-01 00:00:00pages
107-14issue
2eissn
1173-2563issn
1179-1918pii
2523journal_volume
25pub_type
杂志文章abstract:BACKGROUND:NSAIDs are widely used for patients presenting with low back pain. A quick-release formulation of lornoxicam, a potent NSAID from the chemical class of oxicams, offers a faster onset of pain relief compared with the standard tablet formulation. METHODS:Time to onset of pain relief with lornoxicam was compar...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2165/00044011-200626050-00004
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Oxycodone tamper resistant (OTR) is a new extended-release abuse-deterrent formulation providing improvements in the tamper resistant characteristics. This study aimed to investigate the pharmacokinetic properties of the new OTR tablets and evaluate the bioequivalence of oxycodone from OTR and...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-019-00870-w
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Dyslipidaemia is a major cardiovascular risk factor associated with type 2 diabetes mellitus. Saroglitazar (ZYH1) is a novel peroxisome proliferator-activated receptor (PPAR) agonist with predominant PPARα and moderate PPARγ activity. It has been developed for the treatment of dyslipidaemia an...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-013-0128-3
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVE:Central nervous effects of oral anticholinergics may limit the success of incontinence therapy and patient compliance. Only a few studies investigating this topic are available. This study was conducted to determine whether oral anticholinergics alter sleep and psychometric test parameters. DESIGN:Randomised...
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pub_type: 临床试验,杂志文章,多中心研究
doi:10.2165/00044011-200828110-00001
更新日期:2008-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 已发布勘误
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更新日期:2019-07-01 00:00:00
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更新日期:2013-12-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-018-0716-3
更新日期:2019-01-01 00:00:00
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更新日期:1998-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2021-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2021-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2015-07-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-015-0314-6
更新日期:2015-09-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2017-02-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.2165/11539750-000000000-00000
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:The possible adverse or positive effects of levothyroxine treatment among patients with atrial fibrillation have been debated. Atrial fibrillation, levothyroxine treatment, and dementia are common among older adults, yet little is known about the effects of levothyroxine on the development of d...
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pub_type: 杂志文章
doi:10.1007/s40261-018-0740-3
更新日期:2019-02-01 00:00:00
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pub_type:
doi:10.1007/s40261-020-00975-7
更新日期:2021-01-01 00:00:00
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更新日期:2016-04-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
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更新日期:2021-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
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更新日期:2010-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/11595860-000000000-00000
更新日期:2012-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2019-04-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200626100-00003
更新日期:2006-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
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更新日期:2014-09-01 00:00:00
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pub_type: 杂志文章,meta分析,评审
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更新日期:2016-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Dasotraline is a novel inhibitor of dopamine and norepinephrine reuptake currently being investigated in clinical studies for the treatment of attention-deficit/hyperactivity disorder (ADHD). Uniquely, relative to current ADHD medications, dasotraline has a slow absorption and long elimination...
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