Abstract:
PURPOSE:A variety of diagnostic methods are available to validate the performance of population pharmacokinetic models. Internal validation, which applies these methods to the model building dataset and to additional data generated through Monte Carlo simulations, is often sufficient, but external validation, which requires a new dataset, is considered a more rigorous approach, especially if the model is to be used for predictive purposes. Our first objective was to validate a previously published population pharmacokinetic model of darunavir, an HIV protease inhibitor boosted with ritonavir or cobicistat. Our second objective was to use this model to derive optimal sampling strategies that maximize the amount of information collected with as few pharmacokinetic samples as possible. METHODS:A validation dataset comprising 164 sparsely sampled individuals using ritonavir-boosted darunavir was used for validation. Standard plots of predictions and residuals, NPDE, visual predictive check, and bootstrapping were applied to both the validation set and the combined learning/validation set in NONMEM to assess model performance. D-optimal designs for darunavir were then calculated in PopED and further evaluated in NONMEM through simulations. RESULTS:External validation confirmed model robustness and accuracy in most scenarios but also highlighted several limitations. The best one-, two-, and three-point sampling strategies were determined to be pre-dose (0 h); 0 and 4 h; and 1, 4, and 19 h, respectively. A combination of samples at 0, 1, and 4 h was comparable to the optimal three-point strategy. These could be used to reliably estimate individual pharmacokinetic parameters, although with fewer samples, precision decreased and the number of outliers increased significantly. CONCLUSIONS:Optimal sampling strategies derived from this model could be used in clinical practice to enhance therapeutic drug monitoring or to conduct additional pharmacokinetic studies.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Stillemans G,Belkhir L,Vandercam B,Vincent A,Haufroid V,Elens Ldoi
10.1007/s00228-020-03036-2subject
Has Abstractpub_date
2020-11-11 00:00:00eissn
0031-6970issn
1432-1041pii
10.1007/s00228-020-03036-2pub_type
杂志文章abstract::The pharmacokinetics of mexiletine, a Class I antiarrhythmic drug, was investigated in 6 healthy volunteers after single oral doses and 15 min intravenous infusions of 3 mg/kg. Cimetidine and ranitidine are commonly used H2-receptor antagonists, which interact adversely with many drugs, e.g. inhibition of the metaboli...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558298
更新日期:1989-01-01 00:00:00
abstract::In 10 healthy male subjects the pharmacokinetics and haemodynamic effects of sustained-release isosorbide-5-mononitrate 60 mg (IS-5-MN) were studied after oral administration at two different times in the day (08.00 h and 20.00 h). Effects on blood pressure and heart rate after 3 min standing upright were measured in ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315142
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVES:To identify the frequency of CYP2C9*1, *2 and *3 alleles and the genotype of CYP2C9 gene in the Tamilian population. METHODS:The study was conducted on 135 unrelated healthy human volunteers. DNA was extracted from the peripheral leukocytes samples and was analyzed using the polymerase chain reaction (PCR)-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0666-3
更新日期:2003-11-01 00:00:00
abstract:PURPOSE:To aid prescribers in assessing a patient's risk for statin-induced myopathy (SIM), we performed a comprehensive review of currently known risk factors and calculated aggregated odds ratios for each risk factor through a meta-analysis. METHODS:This meta-analysis was done through four phases: (1) Identification...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00228-018-2482-9
更新日期:2018-09-01 00:00:00
abstract:PURPOSE:The incidence of osteoporosis-related fractures will increase substantially over the coming decades as the population ages globally. This has important economic and public health implications, contributing substantially to morbidity and excess mortality in this population. METHODS:When prescribing for older pa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-011-0999-2
更新日期:2011-04-01 00:00:00
abstract:PURPOSE:This exploratory study was aimed at elucidating the pharmacogenetics of regulatory nuclear receptors (PXR, CAR, RXRα and HNF4α) and their implications on docetaxel pharmacokinetics and pharmacodynamics in local Chinese nasopharyngeal cancer patients. METHODS:A total of 59 single nucleotide polymorphisms (SNPs)...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-013-1596-3
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:Case report of a pharmacokinetic interaction between diltiazem and nortriptyline. METHODS:Determination of plasma nortriptyline concentrations by HPLC. Calculation of nortriptyline clearances and half-life by formulae used routinely in therapeutic drug monitoring. RESULTS:The average plasma concentration of...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00203789
更新日期:1996-01-01 00:00:00
abstract:INTRODUCTION:Reimbursement databases are potentially invaluable tools to develop and conduct pharmacoepidemiological studies on drug use. However, two types of factors that may influence the performance of a database can be distinguished: firstly, factors related to the constitution of the database, and secondly, facto...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-010-0819-0
更新日期:2010-07-01 00:00:00
abstract::The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I). The pharmacokinetic parameters of the act...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF02284968
更新日期:1992-01-01 00:00:00
abstract::An analytical procedure for the simultaneous determination of pethidine and its N-Demethylated metabolite, norpethidine, in plasma is described. Pethidine and norpethidine are separated by partition chromatography, converted to the trichloroethyl carbamate with trichloroethyl chloroformate and determined by electron c...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561790
更新日期:1977-01-01 00:00:00
abstract:OBJECTIVE:Losartan was given to subjects with known phenotypes of the polymorphic enzymes CYP2D6 and CYP2C19 to study any possible influence on the metabolism of the drug. METHODS:Plasma concentrations of losartan and E-3174 were studied after oral intake of 50 mg losartan in 24 healthy, male, Swedish Caucasian subjec...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050629
更新日期:1999-06-01 00:00:00
abstract:PURPOSE:Tolvaptan is a selective vasopressin V2 receptor antagonist that can be given orally once daily for treatment of clinically significant hypervolemic and euvolemic hyponatremia (US and Europe) or extracellular volume expansion despite taking other diuretics (Japan). In vitro studies indicated that tolvaptan was ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00228-011-1106-4
更新日期:2012-02-01 00:00:00
abstract::The effect of treatment with diflunisal on the steady-state pharmacokinetics of indomethacin has been studied in 16 healthy volunteers. The steady-state plasma concentration and AUC of indomethacin were significantly increased two- to threefold during treatment with diflunisal and its total clearance and total volume ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558077
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:We have developed a model for integrated medicines management, including tools and activities for medication reconciliation and medication review. In this study, we focus on improving the quality of the discharge summary including the medication report to reduce medication errors in the transition from hospital...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-009-0680-1
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:The European Committee for Human Medicinal Products (CHMP) requested a multinational study with the aim to investigate the risk of acute liver failure (ALF) leading to registration for transplantation in patients exposed to non-steroidal anti-inflammatory drugs (NSAIDs). The method of this multinational, multic...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-012-1357-8
更新日期:2013-03-01 00:00:00
abstract::Procainamide was given to 20 patients with normal renal function as an i.v. bolus of 500 mg followed by 1.0 or 1.5 g eight-hourly by mouth in the form of a slow release preparation (Durules). 97.6 +/- 27.1 (SD)% of the oral procainamide was absorbed, the absorption half life being 1.54 h. The elimination half life fol...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00560459
更新日期:1978-12-01 00:00:00
abstract:BACKGROUND:Monoamine oxidase inhibitors (MAOIs) are uncommonly used due to their high frequency of adverse effects, including tachycardia and hypertension. Recently, there has been renewed interest in the role of this class of drugs in treating a variety of psychiatric disorders. The clinical features of MAOI overdose ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-007-0360-y
更新日期:2007-11-01 00:00:00
abstract::Twenty-four healthy volunteers participated in a study on the disposition of ergotamine following oral and rectal administration. Plasma samples were collected surrounding each dose of medication and a new mass spectrometry method was used for quantitation of the samples. A mean peak plasma concentration of 454 pg/ml ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00541538
更新日期:1986-01-01 00:00:00
abstract::Changes in phenytoin concentrations caused by switching valproate formulations with different absorption rates were retrospectively investigated in eleven epileptic patients receiving treatment with both drugs. Total plasma phenytoin concentrations were measured before and after a standard tablet of valproate was repl...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00202174
更新日期:1995-01-01 00:00:00
abstract::We have studied the pharmacodynamic effects of ramipril, propranolol, and their combination, as well as the effect of propranolol on the pharmacokinetics of ramipril in 12 healthy men (age 24 (SD 6) y, weight 72 (7) kg). Propranolol and placebo, ramipril and placebo, or propranolol and ramipril were given orally for f...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00315392
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:Older people with several chronic conditions require multiple drugs from different classes to be adequately treated. This study aims to: (i) measure medication adherence across multiple conditions and therapeutic drug groups in older community-dwelling patients, and (ii) examine the effect of multimorbidity on ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-017-2388-y
更新日期:2018-03-01 00:00:00
abstract::Postural and isometric handgrip tests were performed on nine patients with panic disorder and 13 patients with major depression before and after treatment with imipramine for a mean duration of 10 weeks. There were significant increases in resting supine heart rate (HR), systolic, diastolic and mean blood pressures (S...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00265972
更新日期:1990-01-01 00:00:00
abstract::The effect of acute and long-term treatment with propranolol on cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2) has been studied in 8 young healthy volunteers. CBF was measured by 133Xe-inhalation and single photon emission computer tomography, and CMRO2 was calculated from the arterio-veno...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315115
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their ratios during pr...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1944-6
更新日期:2015-12-01 00:00:00
abstract:PURPOSE:To investigate possible differences in the time course of vasodilating effects of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in humans. METHODS:We measured forearm blood flow (FBF) by strain gauge plethymography and cyclic GMP spillover during and after intra-arterial infusions of BNP...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-008-0516-4
更新日期:2008-09-01 00:00:00
abstract::The influence of bezafibrate treatment on hepatic cholesterol metabolism was studied in rats and in humans. The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cholesterol acyltransf...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF01409405
更新日期:1991-01-01 00:00:00
abstract::This study investigates the acute haemodynamic effects of Quinapril (CI-906) a new non-sulphydryl angiotensin converting enzyme inhibitor in 15 patients with refractory congestive cardiac failure. There were 14 males and 1 female mean age 59.5 years. After administration of Quinapril there was a significant reduction ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00870978
更新日期:1986-01-01 00:00:00
abstract::The pharmacokinetics of melatonin during the day-time has been studied in 4 healthy subjects after a bolus i.v. injection of 5 or 10 micrograms/person and after a 5 h infusion of 20 micrograms per person in 6 healthy subjects. In addition, a pinealomectomized patient whose nocturnal plasma melatonin had been abolished...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315035
更新日期:1990-01-01 00:00:00
abstract::The kinetics and dynamics of single doses (5 mg p.o.) of the optical isomers of acenocoumarol (R-AC and S-AC) were followed in healthy subjects and the effect on them of cimetidine 800 mg/day was also investigated. The AC enantiomers differed greatly in their pharmacokinetics. The mean residence time (MRT) of R-AC was...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542424
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:To quantify pharmacokinetic (PK) and pharmacodynamic (PD) relationships of various classes of GABAA agonists in healthy volunteers, in order to investigate the sensitivity of the biomarker responses due to differing GABAA-subtype selectivity and to explore the correlation between biomarker responses and side ef...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s00228-015-1918-8
更新日期:2015-10-01 00:00:00