Abstract：
:Half-life is a standard result reported with analysis of pharmacokinetic data. Different definitions such as noncompartmental half-life, terminal half-life, effective half-life, and context-sensitive half-life can yield substantially different estimates of the quantity "half-life." Time to attainment of steady-state conditions is generally derived from (terminal) half-life and therefore sensitive toward the definition of half-life. Thus, estimates of the time to attain steady state must be provided with a precise definition of steady state and the method used for estimation, particularly for drugs with long (terminal) half-life. For clinical purposes, terminal half-life can have limited relevance if drug concentrations in the terminal elimination phase are low. A general rule for which half-life to use is infeasible. While limited accumulation can be negligible if a plateau in pharmacokinetics/pharmacodynamics is reached or with a wide therapeutic window (ie, exposure range), small additional drug accumulation can be highly relevant for drugs with a narrow therapeutic window. Beyond the average, estimation of individual time to attainment of steady state can add highly relevant information about the variability between subjects. Simulations from population models and the use of different definitions of steady state provide an assessment of robustness of the results. The relevance of accurate estimation of time to attainment of steady state is illustrated with cenerimod, an sphingosine-1-phosphate 1 receptor modulator with long half-life currently in clinical development for which estimates of time to steady state ranged from 35 to 110 days with different calculations.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Krause A,Lott D,Dingemanse Jdoi
10.1002/jcph.1701subject
Has Abstractpub_date
2021-01-01 00:00:00pages
82-89issue
1eissn
0091-2700issn
1552-4604journal_volume
61pub_type
杂志文章abstract：:We administered 0.5-and 1.0-mg doses of bumetanide intravenously to eight normal subjects with and without pretreatment with probenecid. Probenecid did not effect either the cumulative response or the time course of response of bumetanide. These results are in contrast to results reported in dogs but consistent with s...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb01772.x
更新日期：1981-07-01 00:00:00
abstract：:In many industrialized nations, the elderly comprise the fastest growing subpopulation and constitute an increasing proportion of the total population compared to other age groups. The elderly use a disproportionately larger amount of health care resources since they experience a higher incidence of disease-related mo...
journal_title：Journal of clinical pharmacology
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doi：
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abstract：:The objective of this study was to evaluate the effect of the acute administration of marijuana (MJ) on cardiovascular (CV) function and CNS pharmacokinetics (PK) of [(15)O]water in occasional (O) versus chronic (C) MJ users. Each subject received four injections of [(15)O]water (one prior and three postsmoking) on tw...
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1976.tb01491.x
更新日期：1976-01-01 00:00:00
abstract：:Raltegravir is a novel HIV-1 integrase inhibitor with potent in vitro activity (95% inhibitory concentration = 33 nM in 50% human serum). In vitro characterization of raltegravir inhibition potential was assessed against a panel of cytochrome P450 (CYP) enzymes. An open-label, 2-period study was conducted to assess th...
journal_title：Journal of clinical pharmacology
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abstract：:A clinical study of bumetanide, a new diuretic, was conducted in outpatients of a cardiology clinic to determine its long-term effectiveness and safety in the treatment of peripheral edema due to congestive heart failure. The drug was administered for at least 24 weeks on a selected group of 34 patients. The patients ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb05685.x
更新日期：1981-11-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1716
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1996.tb04222.x
更新日期：1996-07-01 00:00:00
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更新日期：2008-08-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/00912700122009791
更新日期：2001-01-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1797
更新日期：2020-12-07 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1987.tb03022.x
更新日期：1987-04-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
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更新日期：2019-01-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1989.tb03287.x
更新日期：1989-12-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.419
更新日期：2015-04-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.147
更新日期：2013-10-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb01933.x
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270003261333
更新日期：2004-02-01 00:00:00
abstract：:Data from 58 premarketing studies of the nonsteroidal antiinflammatory drug flurbiprofen were pooled for analyses of adverse drug reactions (ADRs). These studies included 5602 patients treated with flurbiprofen (N = 4123), aspirin (N = 1033), or placebo (N = 446) for varying durations. Diagnoses included rheumatoid ar...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1990.tb03604.x
更新日期：1990-04-01 00:00:00
abstract：:Bioavailability of pioglitazone and metformin, in 2 dose strengths, given either as a fixed-dose combination tablet or as coadministration of commercial tablets (coad), was studied in young healthy subjects in 2 separate studies. In study I (n = 63), single oral doses of 15-mg pioglitazone/500-mg metformin fixed-dose ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,meta分析,随机对照试验
doi：10.1177/0091270006293755
更新日期：2007-01-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
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更新日期：1975-10-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.602
更新日期：2016-03-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
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更新日期：2002-07-01 00:00:00
abstract：:Ofatumumab is a human monoclonal antibody that binds to a unique CD20 epitope on the surface of B lymphocytes, resulting in efficient lysis of CD20-expressing cells via complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. The potential effect of ofatumumab on cardiac repolarization and ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1002/jcph.376
更新日期：2015-01-01 00:00:00
abstract：:A reflectance spectrophotometric method for evaluation of the skin blanching response to topical corticosteroids was evaluated. This blanching response is used, for drug development and regulatory purposes, to assess potency and bioequivalence of topical corticosteroid products. The common method involves the use of a...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb05611.x
更新日期：1993-08-01 00:00:00
