Abstract：
:The half-life of a drug, which expresses a change in concentration in units of time, is perhaps the most easily understood pharmacokinetic parameter and provides a succinct description of many concentration-time profiles. The calculation of a half-life implies a linear, first-order, time-invariant process. No drug perfectly obeys such assumptions, although in practise this is often a valid approximation and provides invaluable quantitative information. Nevertheless, the physiological processes underlying half-life should not be forgotten. The concept of clearance facilitates the interpretation of factors affecting drug elimination, such as enzyme inhibition or renal impairment. Relating clearance to the observed concentration-time profile is not as naturally intuitive as is the case with half-life. As such, these 2 approaches to parameterising a linear pharmacokinetic model should be viewed as complementary rather than alternatives. The interpretation of pharmacokinetic parameters when there are multiple disposition phases is more challenging. Indeed, in any pharmacokinetic model, the half-lives are only one component of the parameters required to specify the concentration-time profile. Furthermore, pharmacokinetic parameters are of little use without a dose history. Other factors influencing the relevance of each disposition phase to clinical end-points must also be considered. In summarising the pharmacokinetics of a drug, statistical aspects of the estimation of a half-life are often overlooked. Half-lives are rarely reported with confidence intervals or measures of variability in the population, and some approaches to this problem are suggested. Half-life is an important summary statistic in pharmacokinetics, but care must be taken to employ it appropriately in the context of dose history and clinically relevant pharmacodynamic end-points.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Wright JG,Boddy AVdoi
10.2165/00003088-200140040-00001keywords:
subject
Has Abstractpub_date
2001-01-01 00:00:00pages
237-44issue
4eissn
0312-5963issn
1179-1926journal_volume
40pub_type
杂志文章abstract：BACKGROUND AND OBJECTIVE:Preterm and term newborn infants show wide interindividual variability (IIV) in pharmacokinetic parameters of gentamicin. More extensive knowledge and use of predictive covariates could lead to faster attainment of therapeutic concentrations and a reduced need for concentration monitoring. This...
journal_title：Clinical pharmacokinetics
pub_type： 临床试验,杂志文章
doi：10.2165/00003088-200948040-00003
更新日期：2009-01-01 00:00:00
abstract：BACKGROUND AND OBJECTIVE:Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. In girls with a low birth weight, and early-normal and rapidly progressive puberty, metformin therapy is capable of modifying this outcome, prolonging pubertal growth, increasing height gain, delaying the age at menarch...
journal_title：Clinical pharmacokinetics
pub_type： 临床试验,杂志文章
doi：10.2165/11593970-000000000-00000
更新日期：2011-11-01 00:00:00
abstract：OBJECTIVE:The objective of this study was to assess the pharmacokinetic and pharmacodynamic behavior of ticagrelor administered either as crushed (in the semi-upright sitting position) or as integral (in the supine position) tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percu...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,随机对照试验
doi：10.1007/s40262-015-0320-0
更新日期：2016-03-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Caspofungin is an echinocandin antifungal agent used as first-line therapy for the treatment of invasive candidiasis. The maintenance dose is adapted to body weight (BW) or liver function (Child-Pugh score B or C). We aimed to study the pharmacokinetics of caspofungin and assess pharmacokineti...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s40262-015-0347-2
更新日期：2016-06-01 00:00:00
abstract：:Over the past few decades, the importance of applying pharmacokinetic principles to the design of drug regimens has been increasingly recognised by clinicians. From the perspective of antimicrobial chemotherapy, an improvement in clinical outcome and/or a reduction in toxicity are of primary interest. Before applicati...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.2165/00003088-199937010-00001
更新日期：1999-07-01 00:00:00
abstract：:Cancer chemotherapy doses are empirical in that the majority are administered at a fixed dose (mg/m2 or mg/kg). One reason for this is the intrinsic sensitivity of the tumour or host cells to one particular chemotherapy agent is unknown. Therefore, the likelihood of response or toxicity is unpredictable a priori. This...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.2165/00003088-199732040-00005
更新日期：1997-04-01 00:00:00
abstract：INTRODUCTION:Neglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of ph...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.1007/s40262-016-0467-3
更新日期：2017-06-01 00:00:00
abstract：:Various pharmacokinetic models, both simple and complex, have been developed to describe the way in which the rate of hepatic elimination of drugs depends on hepatic blood flow, hepatic intrinsic clearance and unbound fraction of drug in blood. A model is necessary because it is not possible to measure the average blo...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.2165/00003088-199018010-00004
更新日期：1990-01-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Bayesian forecasting (BF) methods for tobramycin dose individualisation has not seen widespread clinical adoption, despite being endorsed by clinical practice guidelines. Several freeware and commercial programmes using BF methods are available to support personalised dosing. This study evalua...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s40262-017-0610-9
更新日期：2018-08-01 00:00:00
abstract：:Creatine is a nonessential dietary component that, when supplemented in the diet, has shown physiological benefits in athletes, in animal-based models of disease and in patients with various muscle, neurological and neuromuscular disease. The clinical relevance of creatine supplementation is based primarily on its rol...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.2165/00003088-200342060-00005
更新日期：2003-01-01 00:00:00
abstract：:The critically ill patient occupies an increasing amount of time and bed space in modern hospital practice, and also commands increasing expenditure. Drug therapy in these patients has, in the past, been based on data derived from healthy volunteers, fit anaesthetised patients undergoing minor operative procedures, or...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.2165/00003088-198814060-00003
更新日期：1988-06-01 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
abstract：:Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as ind...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s40262-017-0573-x
更新日期：2018-02-01 00:00:00
abstract：BACKGROUND AND OBJECTIVE:Dalcetrapib, a cholesteryl ester transfer protein (CETP) modulator, is a thioester pro-drug that is rapidly hydrolysed to generate a pharmacologically active thiol. The thiol covalently binds to plasma proteins as mixed disulfides, extensively distributes into plasma lipoprotein fractions, and ...
journal_title：Clinical pharmacokinetics
pub_type： 临床试验,杂志文章
doi：10.1007/s40262-013-0035-z
更新日期：2013-04-01 00:00:00
abstract：:Low-molecular-weight heparins are anticoagulants used in the treatment of thrombosis. They have effectiveness and safety profiles similar to those of unfractionated heparin but are considered an attractive alternative because of their predictable pharmacokinetic characteristics. In this article, we demonstrate the nee...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章
doi：10.2165/11532960-000000000-00000
更新日期：2010-09-01 00:00:00
abstract：:Inpatients (n = 57) on long term prophylaxis with 2 oral phenytoin preparations were followed up via monthly checks of serum drug concentrations. Duplicate serum aliquots were submitted to 2 laboratories, and covariance analysis was used to estimate laboratory error. The laboratory-associated variance of examinations ...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章
doi：10.2165/00003088-199120040-00007
更新日期：1991-04-01 00:00:00
abstract：:Voriconazole is both a substrate and a potent inhibitor of cytochrome P450 (CYP) 3A. It has a high bioavailability and non-linear pharmacokinetics. We investigated the pharmacokinetics and metabolism of 50 mg and 400 mg doses of intravenous and oral voriconazole in 14 healthy volunteers. Concurrently, we determined sy...
journal_title：Clinical pharmacokinetics
pub_type： 临床试验,杂志文章
doi：10.1007/s40262-016-0416-1
更新日期：2016-12-01 00:00:00
abstract：:The disposition of simeprevir (SMV) in humans is characterised by cytochrome P450 3A4 metabolism and hepatic uptake by organic anion transporting polypeptide 1B1/3 (OATP1B1/3). This study was designed to investigate SMV plasma and liver exposure upon oral administration in subjects infected with hepatitis C virus (HCV...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s40262-016-0476-2
更新日期：2017-07-01 00:00:00
abstract：:In the treatment of patients with Parkinson's disease, apomorphine has an established place as a back-up therapy if other antiparkinsonian drugs, such as levodopa and oral dopamine agonists, have not controlled the existing response fluctuations. Apomorphine is a synthetic derivative of morphine, with a totally distin...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.2165/00003088-199937030-00004
更新日期：1999-09-01 00:00:00
abstract：:Serum concentration measurements of antibacterial agents are increasingly used to optimise drug dosage regimens. However, this approach is only justified for drugs with a low therapeutic index and poor predictability of serum concentrations, such as the aminoglycosides, chloramphenicol and vancomycin, whereas the peni...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.2165/00003088-198409060-00001
更新日期：1984-11-01 00:00:00
abstract：:Vemurafenib is an orally administered small-molecule inhibitor of the oncogenic BRAF kinase that is indicated for the treatment of patients with unresectable or metastatic melanoma harbouring BRAF V600 mutations. Vemurafenib is absorbed rapidly after a single oral dose of 960 mg, reaching maximum drug concentration ap...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.1007/s40262-017-0523-7
更新日期：2017-09-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Two phase I drug interaction studies were performed with oral enzalutamide, which is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). METHODS:A parallel-treatment design (n = 41) was used to evaluate the effects of a strong cytochrome P450 (CYP) 2C8 inhib...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1007/s40262-015-0283-1
更新日期：2015-10-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Bosentan is a competitive antagonist on endothelin receptor A and B (ETA and ETB), displacing the endogenous binding partner endothelin-1 (ET-1) from its binding sites. After administration of escalating single doses of 10-750 mg as an intravenous (i.v.) infusion, bosentan showed dose-dependen...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章
doi：10.1007/s40262-017-0534-4
更新日期：2017-12-01 00:00:00
abstract：:Rational pharmacotherapy is dependent upon an understanding of the clinical pharmacokinetic and pharmacodynamic properties of the drugs employed. Although the available data on drug biodisposition and action in the neonate have increased considerably in the last few years, pharmacokinetic-pharmacodynamic interactions ...
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
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
abstract：BACKGROUND AND OBJECTIVES:The likelihood of detecting a therapeutic signal of an effective drug for schizophrenia is impeded by a high placebo effect and by high dropout of patients. Several unsuccessful trials of schizophrenia, at least partly due to highly variable placebo effects, have indicated the necessity for a ...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章
doi：10.2165/11598460-000000000-00000
更新日期：2012-04-01 00:00:00
abstract：:Protein binding of antibacterials in plasma and tissues has long been considered a component of their pharmacokinetic parameters, playing a potential role in distribution, excretion and therapeutic effectiveness. Since the beginning of the 'antibacterial era', this factor has been extensively analysed for all antibact...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.2165/00003088-200241100-00004
更新日期：2002-01-01 00:00:00
abstract：:Antibiotic therapy is one of the main treatments for cystic fibrosis (CF). It aims to eradicate bacteria during early infection, calms down the inflammatory process, and leads to symptom resolution of pulmonary exacerbations. CF can modify both the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of antibiotics,...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.1007/s40262-020-00981-0
更新日期：2021-01-24 00:00:00
abstract：BACKGROUND AND OBJECTIVE:Tegafur is an oral fluorouracil prodrug used in the treatment of colorectal cancer. The aim of this phase II, crossover, bioequivalence study was to compare the pharmacokinetics (primary objective) and tolerability (secondary objective) of tegafur-uracil (UFT) given as three daily doses (tid, r...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,随机对照试验
doi：10.2165/00003088-200746110-00003
更新日期：2007-01-01 00:00:00
abstract：:Pharmacological treatment of patients with Alzheimer's disease is becoming more important, as evidenced by the number of drugs being developed in different countries. It has been shown in the majority of clinical trials that cholinesterase inhibitors, such as tacrine (tetrahydroaminoacridine), are able to induce benef...
journal_title：Clinical pharmacokinetics
pub_type： 杂志文章,评审
doi：10.2165/00003088-199529020-00005
更新日期：1995-08-01 00:00:00
