Abstract：
AIMS:Vancomycin is an important antibiotic for critically ill patients with Gram-positive bacterial infections. Critically ill patients typically have severely altered pathophysiology, which leads to inefficacy or toxicity. Model-informed precision dosing may aid in optimizing the dose, but prospectively validated tools are not available for this drug in these patients. We aimed to prospectively validate a population pharmacokinetic model for purpose model-informed precision dosing of vancomycin in critically ill patients. METHODS:We first performed a systematic evaluation of various models on retrospectively collected pharmacokinetic data in critically ill patients and then selected the best performing model. This model was implemented in the Insight Rx clinical decision support tool and prospectively validated in a multicentre study in critically ill patients. The predictive performance was obtained as mean prediction error and relative root mean squared error. RESULTS:We identified 5 suitable population pharmacokinetic models. The most suitable model was carried forward to a prospective validation. We found in a prospective multicentre study that the selected model could accurately and precisely predict the vancomycin pharmacokinetics based on a previous measurement, with a mean prediction error and relative root mean squared error of respectively 8.84% (95% confidence interval 5.72-11.96%) and 19.8% (95% confidence interval 17.47-22.13%). CONCLUSION:Using a systematic approach, with a retrospective evaluation and prospective verification we showed the suitability of a model to predict vancomycin pharmacokinetics for purposes of model-informed precision dosing in clinical practice. The presented methodology may serve a generic approach for evaluation of pharmacometric models for the use of model-informed precision dosing in the clinic.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Ter Heine R,Keizer RJ,van Steeg K,Smolders EJ,van Luin M,Derijks HJ,de Jager CPC,Frenzel T,Brüggemann Rdoi
10.1111/bcp.14360subject
Has Abstractpub_date
2020-12-01 00:00:00pages
2497-2506issue
12eissn
0306-5251issn
1365-2125journal_volume
86pub_type
杂志文章abstract：:The concentration of chloroquine (CQ), dapsone (DDS) and pyrimethamine (PYR) in plasma and milk were measured following the coadministration of a single dose of chloroquine and Maloprim to lactating women. The milk to plasma area under the concentration-time curve (AUC) ratio ranged from 1.96 to 4.26 for CQ, 0.22 to 0...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1986.tb02967.x
更新日期：1986-12-01 00:00:00
abstract：:1 Benzodiazepines are regarded as pure anxiolytics, and their value in the treatment of depression is controversial. Nevertheless, symptoms of anxiety and depression coexist in patients with endogenous or neurotic depression, and clinical trials indicate that depressed patients respond better to a benzodiazepine-tricy...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1981.tb01835.x
更新日期：1981-01-01 00:00:00
abstract：:1. The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind, placebo-controlled, randomised crossover study. 2. Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin, 40 mg day-1 pravastatin or placebo for 4 weeks, separated by a 4...
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.1365-2125.1994.tb04268.x
更新日期：1994-03-01 00:00:00
abstract：:In many endoscopy units midazolam is replacing diazepam as the intravenous sedative of first choice. Midazolam is approximately twice as potent as diazepam. Although generally considered a safe drug, there have been a number of recent reports, particularly in the elderly, of the drug causing hypotension, respiratory d...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1987.tb03037.x
更新日期：1987-02-01 00:00:00
abstract：:1. The cardiovascular responses of mianserin hydrochloride and tricyclic antidepressant drugs were investigated using non-invasive methods of cardiac investigation. A study of the interaction of mianserin and antihypertensive drug therapy is reported. 2. In six normal volunteers, mianserin hydrochloride 20 mg was show...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1978-01-01 00:00:00
abstract：AIMS:QTc interval-prolonging drugs have been linked to cardiac arrhythmias, cardiac arrest and sudden death. In this study we aimed to quantify the risk of cardiac arrest associated with the use of non-antiarrhythmic QTc-prolonging drugs in an academic hospital setting. METHODS:We performed a case-control study in whi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02722.x
更新日期：2007-02-01 00:00:00
abstract：:Residual effects of brotizolam (0.25 mg) and flurazepam (30 mg) were studied in healthy young adults. Performance and subjective assessments were observed from 7 to 8 h after overnight ingestion, and effects were compared with that of placebo. Visuo-motor coordination, visuo-mental processing time, visuo-motor reactio...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1983.tb02309.x
更新日期：1983-01-01 00:00:00
abstract：AIMS:To develop a population pharmacokinetic model for lopinavir in combination with ritonavir, in which the interaction between both drugs was characterized, and in which relationships between patient characteristics and pharmacokinetics were identified. METHODS:The pharmacokinetics of lopinavir in combination with r...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2005.02455.x
更新日期：2005-10-01 00:00:00
abstract：:1. alpha-Bromoisovalerylurea (BIU) is a racemic drug that is metabolized by glutathione conjugation. The urinary excretion of the separate diastereomeric mercapturates formed from (S)- and (R)-BIU in healthy young human volunteers was investigated. 2. A pronounced stereoselectivity was observed: the mercapturate forme...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb05407.x
更新日期：1989-08-01 00:00:00
abstract：AIMS:Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients. METHODS:We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echo...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1111/bcp.13895
更新日期：2019-06-01 00:00:00
abstract：AIMS:The aims of the study were to characterize the pharmacokinetics (PK) of selumetinib (AZD6244; ARRY-142886), a mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor in clinical development for various indications, and its N-desmethyl metabolite in healthy volunteers, and evaluate clinically important covariat...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13404
更新日期：2018-01-01 00:00:00
abstract：:1. Mono(ADP-ribosyl)transferase activity has been identified on the external surface of human polymorphonuclear neutrophil leucocytes (PMNs). The enzyme is released from the plasma membrane by phosphoinositide-specific phospholipase C, suggesting a glycosylphosphatidylinositol (GPI) linkage of the enzyme to the plasma...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1996.37014.x
更新日期：1996-07-01 00:00:00
abstract：AIMS:This study was conducted to determine whether atenolol was able to decrease BP level and mitigate BP increase during dynamic resistance exercise performed at three different intensities in hypertensives. METHODS:Ten essential hypertensives (systolic/diastolic BP between 140/90 and 160/105mmHg) were blindly studie...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2010.03742.x
更新日期：2010-11-01 00:00:00
abstract：:Ten volunteers carried a 10 mg 24 h -1 transdermal glyceryl trinitrate (GTN) patch for 24 h before moderate exercise. Plasma GTN-concentration increased significantly (P less than 0.05) by 19% to peak value at 15 min. Two hours after patch renewal repeat exercise increased GTN concentration by 56% (P less than 0.001)....
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb05582.x
更新日期：1991-05-01 00:00:00
abstract：:1. Eight volunteers received in randomized order two 30 microliters drops of either 1% w/v cyclopentolate hydrochloride or a corresponding amount of cyclopentolate polygalacturonate in saline or in acetate buffer in one eye. Cyclopentolate concentrations in plasma were measured by a radioreceptor assay. 2. Peak plasma...
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.1365-2125.1993.tb04173.x
更新日期：1993-05-01 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：WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Human pregnane X receptor (PXR/NR1I2) is a key regulator of cytochrome P450 3A4. To date, there are 198 reported SNPs for the human PXR/NR1I2 gene. Some of these SNPs are found to affect the inducing ability of PXR to CYP3A4. WHAT THIS STUDY ADDS:This study, for the first time,...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2008.03344.x
更新日期：2009-02-01 00:00:00
abstract：:1 Herbal preparations containing atropine-like alkaloids are marketed as proprietory asthma remedies, typically in the form of cigarettes. 2 This randomised, cross-over study compares in six healthy volunteers the pharmacological effects caused by smoking a standard, medium tar, tobacco cigarette or a herbal cigarette...
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.1365-2125.1980.tb01793.x
更新日期：1980-11-01 00:00:00
abstract：:Individual and population differences in polymorphic cytochrome P450 enzyme function have been known for decades. The biological significance of these differences has now been deciphered with regard to drug metabolism, action and toxicity as well as disposition of endogenous substrates, including neuroactive compounds...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12227
更新日期：2014-04-01 00:00:00
abstract：:1. A double-blind, four period crossover study was undertaken to test for an interaction between single oral doses of nifedipine retard (20 mg) and lisinopril (20 mg) in normal subjects. 2. Side effects with both drugs were mild and the incidence was additive. 3. Blood pressure (BP) was lowered by nifedipine for 4 h, ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1988.tb03308.x
更新日期：1988-03-01 00:00:00
abstract：:One hundred different drug advertisements from each of seven leading medical journals have been assessed. Information about drug interactions, adverse reactions, mode of action, absorption, distribution, metabolism, excretion and cost was seldom provided in UK journals. A requirement should exist that drug advertiseme...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1976.tb00358.x
更新日期：1976-12-01 00:00:00
abstract：:The fall in blood pressure produced by captopril is not accompanied by a compensatory tachycardia. Angiotensin converting enzyme may participate in the metabolism of endogenous opioids and these substances can lower blood pressure without reflex tachycardia. It is therefore possible that the hypotensive effect of capt...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1984.tb02408.x
更新日期：1984-06-01 00:00:00
abstract：:1. The purpose of this study was to evaluate possible changes in brain morphology and evoked potentials associated with daily administration of 300 mg kg-1 vigabatrin in dogs. 2. Somatosensory evoked potentials (SEP) and auditory evoked potentials (AEP) were recorded at baseline and weekly for 12 weeks of treatment an...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb03462.x
更新日期：1989-01-01 00:00:00
abstract：AIMS:This paper describes the pharmacokinetics and effects of propofol in short-term sedated paediatric patients. METHODS:Six mechanically ventilated children aged 1-5 years received a 6 h continuous infusion of propofol 6% at the rate of 2 or 3 mg kg-1 h-1 for sedation following cardiac surgery. A total of seven arte...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2002.01652.x
更新日期：2002-10-01 00:00:00
abstract：:1. A rapid intravenous bolus injection of 4.0 g Magnapen (which contains 2.0 g of ampicillin and 2.0 g of flucloxacillin) was to seven patients undergoing total hip replacement immediatly before induction of general anesthesia. Postoperatively the patients patients received 2.0 g Magnapen by intramuscular injection ev...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1978.tb00838.x
更新日期：1978-08-01 00:00:00
abstract：AIMS:This double-blind, randomized, four-period, two-way crossover study was conducted to evaluate the acute effects of oral sildenafil (100-mg single dose) on sperm motility, count, density, morphology and vitality as well as ejaculate volume and viscosity in healthy male subjects. The concentrations of sildenafil and...
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.0306-5251.2001.00033.x
更新日期：2002-01-01 00:00:00
abstract：AIM:Pharmacokinetics of small molecule kinase inhibitors (KIs) used in cancer treatment may alter with increasing age, but results are conflicting. This study aims to compare exposure to KIs between older and younger patients (≥70 and <70 years) in clinical practice. METHODS:KI plasma concentrations of routinely treat...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13725
更新日期：2018-12-01 00:00:00
abstract：:The thermogenic beta 3-adrenoceptor agonist BRL 26830A has been shown to increase weight loss in dieting subjects but tremor was a frequent adverse effect. We have investigated the magnitude and nature of this tremor after a single oral dose in 18 subjects. Two complementary techniques were used to attach the recordin...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1990.tb03821.x
更新日期：1990-10-01 00:00:00
abstract：:1 A double-blind trial with parallel treatment groups was conducted to compare the safety and efficacy of mianserin with amitriptyline. 2 This was a six week trial with weekly visits. Measurements at each visit included: 21 item Hamilton Depression (HAMD) Scale. Clinical Global Impression (CGI) Scale and Treatment Eme...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1983.tb05870.x
更新日期：1983-01-01 00:00:00
abstract：:Aims We investigated whether venoconstriction by α-adrenoceptor stimulation, and venodilation by β-adrenoceptor stimulation and nitroglycerin are altered in patients with diabetes mellitus (DM). Methods Eight male patients with non insulin-dependent DM and eight age-matched control subjects were included. The patients...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1999.00915.x
更新日期：1999-04-01 00:00:00
