Abstract:
:Dilevalol and labetalol are examples of a growing number of new beta-blockers which combine nonselective beta-adrenoceptor antagonism with vasodilator activity. Dilevalol is one of the 4 stereoisomers of labetalol, and is estimated to form approximately 25% of the racemic drug. Labetalol itself is an alpha 1-antagonist but dilevalol, which has negligible affinity for alpha-receptors, exerts its vasodilator effect via beta 2-agonism. Both drugs are rapidly and completely absorbed in 60 to 90 min and subject to extensive first-pass hepatic metabolism; the average bioavailability after oral administration is around 20 to 35%, and there is wide interindividual variability in plasma drug concentrations and dosage requirements. The volume of distribution of dilevalol (17 to 25 L/kg) is higher than that reported for labetalol (3 to 16 L/kg), although both drugs are concentrated in the extravascular compartment. Correspondingly, the elimination half-life of dilevalol at steady-state is around 15h compared with 8h for labetalol. There is evidence that the pharmacokinetics of dilevalol change (a reduction in clearance) in translation from single-dose to long term therapy. There is no clinically significant effect of age on the steady-state disposition of either drug and the pharmacokinetics of labetalol appear to be unchanged during pregnancy. Although there is a linear relationship between dose and area under the concentration-time curve, early studies found no evidence of a simple relationship between dose or plasma drug concentration and the fall in blood pressure. However, an integrated pharmacokinetic-pharmacodynamic model has been used to correlate concentrations of both drugs with reductions in systolic and diastolic blood pressure in individuals. This approach derives a mathematical description of antihypertensive response which integrates pharmacokinetic and pharmacodynamic information and also takes account of placebo effects and changes in drug concentration and blood pressure during the dosage interval. The pharmacokinetic-pharmacodynamic relationships of labetalol are characterised by a linear model. For example, in a group of healthy volunteers, the 'responsiveness' to labetalol was -0.19mm Hg/micrograms/L. In contrast, the relationships of dilevalol are best described by a Langmuir maximum effect model, and so individual responses to short and long term treatment have been quantified by the concentration-effect parameters of maximum effect and drug concentration required to produce 50% of this.(ABSTRACT TRUNCATED AT 400 WORDS)
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Donnelly R,Macphee GJdoi
10.2165/00003088-199121020-00002subject
Has Abstractpub_date
1991-08-01 00:00:00pages
95-109issue
2eissn
0312-5963issn
1179-1926journal_volume
21pub_type
杂志文章,评审abstract:BACKGROUND AND OBJECTIVE:Vicriviroc is a small-molecule CCR5 antagonist currently in development for the treatment of HIV in patients on a regimen containing a ritonavir-boosted protease inhibitor. As renal disease and renal dysfunction are prevalent in the HIV-infected population, patients with varying degrees of rena...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.2165/11319470-000000000-00000
更新日期:2010-06-01 00:00:00
abstract::First-pass elimination takes place when a drug is metabolised between its site of administration and the site of sampling for measurement of drug concentration. Clinically, first-pass metabolism is important when the fraction of the dose administered that escapes metabolism is small and variable. The liver is usually ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198409010-00001
更新日期:1984-01-01 00:00:00
abstract::The intracellular pharmacokinetics of the different classes of antimicrobials into surrogate markers of tissue accumulation (alveolar macrophages and/or total alveolar cells collected by means of bronchoalveolar lavage or peripheral white blood cells) was reviewed. The aim of this review was to discuss the clinical im...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-017-0572-y
更新日期:2018-02-01 00:00:00
abstract::Drug-drug, drug-formulation and drug-meal interactions are of clinical concern for orally administered drugs that possess a narrow therapeutic index. This review presents the current status of information regarding interactions which may influence the gastrointestinal (GI) absorption of orally administered drugs. Abso...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199936030-00004
更新日期:1999-03-01 00:00:00
abstract::The combination of hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil and oxaliplatin with intravenous cetuximab has safely achieved prolonged survival in colorectal cancer patients with extensive liver metastases and prior treatment. Systemic exposure to the drugs or their main metabolites was determined dur...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,多中心研究
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-017-0590-9
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
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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
doi:10.1007/s40262-014-0149-y
更新日期:2014-08-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0420-5
更新日期:2016-12-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,meta分析
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更新日期:2017-10-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199937001-00004
更新日期:1999-01-01 00:00:00
abstract:OBJECTIVE:To study the pharmacokinetics of micafungin in intensive care patients and assess pharmacokinetic (PK) target attainment for various dosing strategies. METHODS:Micafungin PK data from 20 intensive care unit patients were available. A population-PK model was developed. Various dosing regimens were simulated: ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0509-5
更新日期:2017-10-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199223040-00003
更新日期:1992-10-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199222040-00006
更新日期:1992-04-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Numerous population pharmacokinetic (PK) models of tacrolimus in adult transplant recipients have been published to characterize tacrolimus PK and facilitate dose individualization. This study aimed to (1) investigate clinical determinants influencing tacrolimus PK, and (2) identify areas requ...
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pub_type: 杂志文章,评审
doi:10.1007/s40262-020-00922-x
更新日期:2020-11-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198308010-00004
更新日期:1983-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 已发布勘误
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更新日期:2019-09-01 00:00:00
abstract::Histamine H2-receptor antagonists are a unique class of compounds. Pharmacologically they are characterised as a family by their ability to inhibit the secretion of gastric acid, and kinetically they are classified as a family by their similarity in absorption, distribution and elimination. All the H2-receptor antagon...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199120030-00004
更新日期:1991-03-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11596990-000000000-00000
更新日期:2012-03-01 00:00:00
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doi:10.2165/00003088-200241020-00002
更新日期:2002-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200544040-00002
更新日期:2005-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200645010-00003
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:To investigate the effect of concomitant administration of dairy products on the pharmacokinetics and tolerability of moxifloxacin. DESIGN:This was a single-centre, randomised, controlled, nonblinded, 2-way crossover study in healthy volunteers. PARTICIPANTS:12 healthy men (aged 25 to 46 years) were enrolle...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200140001-00005
更新日期:2001-01-01 00:00:00
abstract::The steady-state plasma concentrations of antipsychotic drugs show large interpatient variations but remain relatively stable from day to day in each individual patient. Monitoring of antipsychotic drug concentrations in plasma might be of value provided the patients are treated with only 1 antipsychotic drug. Some st...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198611010-00003
更新日期:1986-01-01 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:2001-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Abemaciclib, a dual inhibitor of cyclin-dependent kinases 4 and 6, has demonstrated clinical activity in a number of different cancer types. The objectives of this study were to characterize the pharmacokinetics of abemaciclib in cancer patients using population pharmacokinetic (popPK) modelin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究
doi:10.1007/s40262-017-0559-8
更新日期:2018-03-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-018-0725-7
更新日期:2019-05-01 00:00:00
abstract:OBJECTIVE:To analyse the influence of covariates on the apparent clearance (CL) of tacrolimus in paediatric liver transplant recipients being converted from cyclosporin to tacrolimus. DESIGN:Retrospective modelling study. PATIENTS AND PARTICIPANTS:18 children, 13 girls and 5 boys, aged 4 months to 16 years (median 9....
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200140010-00005
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
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更新日期:2017-06-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199018060-00002
更新日期:1990-06-01 00:00:00