Abstract：
AIM:Lamivudine is used as first line therapy in HIV-infected children. Yet, like many other paediatric drugs, its dose rationale has been based on limited clinical data, without thorough understanding of the effects of growth on drug disposition. Here we use lamivudine to show how a comprehensive population pharmacokinetic model can account for the influence of demographic covariates on exposure (i.e. AUC and Cmax ). METHODS:Data from three paediatric trials were used to describe the pharmacokinetics across the overall population. Modelling was based on a non-linear mixed effects approach. A stepwise procedure was used for covariate model building. RESULTS:A one compartment model with first order elimination best described the pharmacokinetics of lamivudine in children. The effect of weight on clearance (CL) and volume of distribution (V) was characterized by an exponential function, with exponents of 0.705 and 0.635, respectively. For a child with median body weight (17.6 kg), CL and V were 16.5 (95% CI 15.2, 17.7) l h⁻¹ and 46.0 (95% CI 42.4, 49.5) l, respectively. There were no differences between formulations (tablet and solution). The predicted AUC(0,12 h) after twice daily doses of 4 mg kg⁻¹ ranged from 4.44 mg l⁻¹ h for children <14 kg to 7.25 mg l⁻¹ h for children >30 kg. CONCLUSIONS:The use of meta-analysis is critical to identify the correct covariate-parameter relationships, which must be assessed before a model is applied for predictive purposes (e.g. defining dosing recommendations for children). In contrast to prior modelling efforts, we show that the covariate distribution in the target population must be considered.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Piana C,Zhao W,Adkison K,Burger D,Jacqz-Aigrain E,Danhof M,Della Pasqua Odoi
10.1111/bcp.12247subject
Has Abstractpub_date
2014-05-01 00:00:00pages
861-72issue
5eissn
0306-5251issn
1365-2125journal_volume
77pub_type
杂志文章abstract：:1. The pharmacokinetics and pharmacodynamics of intranasal (IN) and oral 1-deamino-8-D-arginine vasopressin (DDAVP) were compared in 10 Chinese adults with central diabetes insipidus previously controlled on IN DDAVP. This was followed by comparison of the acute pharmacodynamics of commonly used oral preparations (con...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1996.39914.x
更新日期：1996-09-01 00:00:00
abstract：AIMS:To investigate the driving forces behind increasing utilization of cardiovascular drugs. METHODS:Using register data, all Danish residents as of 1 January 1996 were followed until 2006. Cohort members were censored at death or emigration. Cardiovascular drug utilization on the individual level was traced, applyin...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1111/j.1365-2125.2008.03282.x
更新日期：2008-12-01 00:00:00
abstract：:1. The three dimensional requirements for inhibition of ACE (angiotensin converting enzyme) were investigated in order to facilitate design of a more potent and selective antihypertensive agent. 2. All compounds designed possessed a bicyclic unit incorporating carboxylate and amidic carbonyl groups together with a thi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb03474.x
更新日期：1989-01-01 00:00:00
abstract：AIMS:Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and probenecid at renal and nonrenal sites. METHODS:A randomized, two-way crossover stud...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2009.03564.x
更新日期：2010-02-01 00:00:00
abstract：AIMS:To assess the antihistaminic activity of levocetirizine and fexofenadine 2 h and 24 h after drug administration using facial thermography and to compare the results with those using well-established parameters of antihistaminic activity in the nose and skin. METHODS:This was a randomized, double-blind, three-trea...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2006.02647.x
更新日期：2006-08-01 00:00:00
abstract：:High consumption of irrational fixed-dose combination (FDC) antibiotics may pose a threat of antimicrobial resistance. In India, ampicillin-cloxacillin was the second highest sold FDC antibiotic behind amoxicillin and clavulanic acid. There remain, however, questions about its efficacy and safety and a lack of regulat...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14711
更新日期：2020-12-23 00:00:00
abstract：:In a double-blind trial the effects on ventilatory function (FEV1), heart rate and blood pressure of oral pirbuterol and oral salbutamol in various single doses were studied in ten patients with chronic asthma. Pirbuterol (15 mg) and salbutamol (4 mg) produced equal peak levels of bronchodilatation. There was no signi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1976.tb04881.x
更新日期：1976-08-01 00:00:00
abstract：:Children are not small adults. However, the main thesis of this review will be that children's responses to drugs have much in common with the responses in adults and indeed in other mammals. Often, it is assumed that drug effects differ in children but in reality this perception often arises because the drugs have no...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.2005.02445.x
更新日期：2005-06-01 00:00:00
abstract：:All beta-adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta-adrenoceptor blocking drugs ...
journal_title：British journal of clinical pharmacology
pub_type： 历史文章,杂志文章,评审
doi：10.1111/j.1365-2125.1978.tb01644.x
更新日期：1978-05-01 00:00:00
abstract：AIMS:Formoterol is a beta2-adrenoceptor agonist marketed as a racemic mixture of the active (R; R)- and inactive (S; S)-enantiomers (rac-formoterol). The drug produces prolonged bronchodilation by inhalation but there is significant interpatient variability in duration of effect. Previous work has shown that in humans ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2000.00133.x
更新日期：2000-02-01 00:00:00
abstract：:1 The acute and chronic (8 weeks) haemodynamic responses to oral flosequinan have been investigated in 12 male patients of mean age 58.9 years with congestive heart failure of N.Y.H.A. classes II and III. 2 Flosequinan 125 mg orally significantly reduced right atrial pressure, pulmonary artery pressure and pulmonary w...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1993.tb00412.x
更新日期：1993-12-01 00:00:00
abstract：AIMS:Establishing a pharmacological challenge model could yield an important tool to understand the complex role of the nicotinic cholinergic system in cognition and to develop novel compounds acting on the nicotinic acetylcholine receptor. METHODS:This randomized, double-blind, double-dummy, placebo-controlled, four-...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13507
更新日期：2018-05-01 00:00:00
abstract：:1. We have investigated the effect of repeated s.c. Org 10172 (a low molecular weight heparinoid; Lomoparan) treatment (1000 anti-Xa units twice daily for 5 days) on antipyrine (500 mg orally) metabolism, and the effect of enzyme induction by pentobarbitone (100 mg for 12 days) on the pharmacokinetics and pharmacodyna...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb05608.x
更新日期：1991-07-01 00:00:00
abstract：:The effects of single doses of anhydrous caffeine (250 mg and 500 mg) and placebo on physiological, psychological measures and subjective feelings were studied in a double-blind, cross-over study in nine healthy subjects who had abstained from caffeine-containing beverages for 24 h before each occasion. Caffeine and c...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1986.tb02883.x
更新日期：1986-07-01 00:00:00
abstract：AIMS:There is a trend for more flexibility in timing of evidence generation in relation to marketing authorization, including the option to complete phase III trials after authorization or not at all. This paper investigated the relation between phase II and III clinical trial efficacy in oncology. METHODS:All oncolog...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14237
更新日期：2020-07-01 00:00:00
abstract：AIMS:To compare the effects of nabumetone and meloxicam, two cyclo-oxygenase-2 (COX-2) preferential nonsteroidal anti-inflammatory drugs (NSAIDs), on platelet COX-1 activity and platelet function. METHODS:Twelve healthy volunteers (3 male, 9 female, median age 22 years) participated in an open, randomized, cross-over ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.2002.01605.x
更新日期：2002-06-01 00:00:00
abstract：AIMS:The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN 50 mg enteric coated tablets. METHODS:Diclo...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2005.02484.x
更新日期：2005-11-01 00:00:00
abstract：:The plasma concentration-response relationships of oral and intravenous pindolol and propranolol have been studied in a group of eight healthy male subjects who received each dosage form in a randomized single-blind cross-over manner. Despite similar elimination half-lives, the duration of action of pindolol was longe...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1985.tb05088.x
更新日期：1985-10-01 00:00:00
abstract：AIMS:5-HT1B-receptor mediated vasoconstriction of cranial arteries is a potential mechanism by which 5-HT1B/1D-receptor agonists such as sumatriptan produce their antimigraine effects. 5-HT1B-receptors exist in other blood vessels which may give rise to unwanted vascular effects. Therefore we examined the distribution ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.0306-5251.2001.01536.x
更新日期：2002-03-01 00:00:00
abstract：AIMS:To explore longitudinal changes in the number and type of medicines used among older people who experience polypharmacy. METHODS:We used pharmaceutical claims for a 10% sample of Australian Pharmaceutical Benefits Scheme beneficiaries to identify people aged 70 years and older who were exposed to 5 or more medici...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14504
更新日期：2020-07-31 00:00:00
abstract：AIM:Drug-drug interactions between antimalarial and antiretroviral drugs may influence antimalarial treatment outcomes. The aim of this study was to investigate the potential drug-drug interactions between the antimalarial drugs, lumefantrine, artemether and their respective metabolites desbutyl-lumefantrine and dihydr...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/bcp.12529
更新日期：2015-04-01 00:00:00
abstract：:Activation of mu opioid receptors on sensory nerves in the lung represents an attractive mechanism for reducing cough and reflex bronchoconstriction. We have examined the effect of the peptide 443C81, a peripherally acting mu opioid agonist, on the cough and reflex increase in respiratory resistance (Rrs) produced by ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1991.tb03966.x
更新日期：1991-11-01 00:00:00
abstract：:Highly active antiretroviral therapy is recommended for HIV-infected pregnant women to prevent mother-to-child transmission. The specific physiological background induced by pregnancy leads to significant changes in maternal pharmacokinetics, suggesting potential variability in plasma concentrations of antiretrovirals...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.2008.03220.x
更新日期：2008-08-01 00:00:00
abstract：:Pharmacogenetic research dedicated to the investigation of inherited factors that influence drug response has produced exciting results over the past decade. Adding to the knowledge that genetic variation in metabolic enzymes may cause drug-related adverse reactions, recent studies indicate that variation in neurotran...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1046/j.1365-2125.2002.01679.x
更新日期：2002-10-01 00:00:00
abstract：:1. Nitric oxide is recognised as an important biological mediator, which is thought to be involved in cardiovascular homeostasis. The purpose of this study was to investigate the effects of basal nitric oxide synthesis on cardiac function in man, by blocking nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1995.tb04550.x
更新日期：1995-10-01 00:00:00
abstract：AIMS:To determine the frequency with which the selective serotonin re-uptake inhibitor (SSRI) antidepressants are used as add-on therapy to the tricyclic antidepressants (TCA) rather than as replacement therapy. METHODS:The data analysed were profiles of prescription records by date of supply to the patient. From with...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2001.01319.x
更新日期：2001-01-01 00:00:00
abstract：AIMS:The goal of this study was to determine the frequencies of important allelic variants in the TPMT, NAT2, GST, SULT1A1 and MDR-1 genes in the Egyptian population and compare them with the frequencies in other ethnic populations. METHODS:Genotyping was carried out in a total of 200 unrelated Egyptian subjects. TPMT...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2003.01786.x
更新日期：2003-06-01 00:00:00
abstract：AIMS:Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care p...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2008.03273.x
更新日期：2008-11-01 00:00:00
abstract：:1. Relative rates of absorption of enteric and non-enteric preparations of prednisolone were measured in five renal transplant recipients. 2. The absorption of the enteric coated preparation is delayed and the peak plasma concentration is much lower than that attained using the same dose of the uncoated material. 3. T...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1975.tb02777.x
更新日期：1975-08-01 00:00:00
abstract：:We have introduced to the course in pharmacology for medical students a simple human experiment that demonstrates the efficacy of activated charcoal in gastrointestinal drug binding. Sixty-one students were given 40 mg frusemide with water, water only, or 40 mg frusemide and 8 g activated charcoal with water either im...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1990.tb03805.x
更新日期：1990-09-01 00:00:00
