Abstract:
:The classic approach to describe the pharmacological response to a drug is to analyse its concentration-effect relationship, using a variety of possible models such as maximum effect (Emax) models or sigmoid Emax models. The aim of this review is to discuss an alternative way of describing the pharmacological effect in terms of effect per unit of drug concentration, instead of simple effect. This variable is called efficiency, analogous with concepts used in other fields. The pharmacodynamic model for efficiency is derived from the sigmoid Emax model and is dependent on the same parameters. Since the sigmoid Emax model incorporates 'the law of diminishing returns', requiring ever higher concentrations to increase the effect by a given percentage, efficiency is bound to decrease with increasing concentrations. However, as a mathematical consequence of its derivation from the sigmoid Emax model, efficiency also has a maximum value, which can be expressed as a function of the slope factor (s) and drug concentration associated with half the maximum effect (C50), provided that the slope factor is greater than 1. The efficiency concept is potentially applicable to all drugs and particularly useful for those that follow concentration-effect relationships according to Emax or sigmoid Emax models. Most experience has been obtained with loop diuretics, especially with furosemide (frusemide). Slow administration of furosemide, leading to slow excretion of the drug, has been shown, in many studies, to significantly increase the total diuretic effect per amount of drug recovered in urine. In this review, some examples of the applicability of the efficiency concept to other drugs, such as antibacterials, opioids and antineoplastics, are discussed. In addition to pharmacodynamically varying efficiency, other saturable processes, such as the formation of active metabolites and saturable transport, may form a basis for the application of the efficiency concept. The efficiency of a drug dosage may also be influenced by tolerance and counter-regulation produced by the drug. All these factors contribute to schedule dependency. It is concluded that the shape of the time course of drug presentation to its site of action is an independent determinant of overall response. The possibility of adjusting the drug input profile to maximise therapeutic effect per dose and to separate cumulated therapeutic from cumulated adverse effects should be considered in designing administration schedules and in drug development.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Alván G,Paintaud G,Wakelkamp Mdoi
10.2165/00003088-199936050-00005keywords:
subject
Has Abstractpub_date
1999-05-01 00:00:00pages
375-89issue
5eissn
0312-5963issn
1179-1926journal_volume
36pub_type
杂志文章,评审abstract::With the aging population and its rapidly increasing prevalence, dementia has become an important public health concern in developed and developing countries. To date, the pharmacological treatment is symptomatic and based on the observed neurotransmitter disturbances. The four most commonly used drugs are donepezil, ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-013-0038-9
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abstract::The pharmacokinetics of metoprolol have been studied in a group of patients with varying degrees of renal impairment and in healthy subjects after administration of 20 mg of metoprolol tartrate intravenously and 50 mg orally in a single dose and during steady-state conditions. There were no significant differences in ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198005020-00004
更新日期:1980-03-01 00:00:00
abstract::The effects of anaesthesia and surgery on the pharmacokinetics of ketobemidone were studied in 12 patients. Plasma ketobemidone concentrations were assayed with a mass-fragmentographic method. The peroperative Vd(area) was 5.9 +/- 2.6L/kg and the terminal half-life was 3.9 +/- 1.7 h. In the postoperative period Vd(are...
journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-198207030-00005
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/11586040-000000000-00000
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doi:10.1007/s40262-020-00883-1
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200645030-00004
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journal_title:Clinical pharmacokinetics
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更新日期:1994-04-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-016-0389-0
更新日期:2016-09-01 00:00:00
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journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-198308020-00004
更新日期:1983-03-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
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journal_title:Clinical pharmacokinetics
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更新日期:2016-03-01 00:00:00
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journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-200140060-00006
更新日期:2001-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198814040-00001
更新日期:1988-04-01 00:00:00
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journal_title:Clinical pharmacokinetics
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更新日期:1997-03-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200847080-00001
更新日期:2008-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
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更新日期:2017-11-01 00:00:00
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journal_title:Clinical pharmacokinetics
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journal_title:Clinical pharmacokinetics
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Clinical pharmacokinetics
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更新日期:2018-07-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1999-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199528030-00002
更新日期:1995-03-01 00:00:00
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journal_title:Clinical pharmacokinetics
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doi:10.1007/s40262-018-00733-1
更新日期:2019-07-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
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更新日期:2003-01-01 00:00:00
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更新日期:2016-10-01 00:00:00
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更新日期:2014-06-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
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abstract:BACKGROUND AND OBJECTIVE:Oral levodopa-carbidopa (LC-oral) treatment in advanced Parkinson's disease (PD) is associated with motor complications due to large fluctuations in levodopa plasma concentrations. Levodopa-carbidopa intestinal gel (LCIG) provides individualized continuous levodopa-carbidopa delivery through in...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-015-0265-3
更新日期:2015-09-01 00:00:00