Abstract:
AIMS:Drug disposition in children may vary from adults due to age-related variation in drug metabolism. Microdose studies present an innovation to study pharmacokinetics (PK) in paediatrics; however, they should be used only when the PK is dose linear. We aimed to assess dose linearity of a [14 C]midazolam microdose, by comparing the PK of an intravenous (IV) microtracer (a microdose given simultaneously with a therapeutic midazolam dose), with the PK of a single isolated microdose. METHODS:Preterm to 2-year-old infants admitted to the intensive care unit received [14 C]midazolam IV as a microtracer or microdose, followed by dense blood sampling up to 36 hours. Plasma concentrations of [14 C]midazolam and [14 C]1-hydroxy-midazolam were determined by accelerator mass spectrometry. Noncompartmental PK analysis was performed and a population PK model was developed. RESULTS:Of 15 infants (median gestational age 39.4 [range 23.9-41.4] weeks, postnatal age 11.4 [0.6-49.1] weeks), 6 received a microtracer and 9 a microdose of [14 C]midazolam (111 Bq kg-1 ; 37.6 ng kg-1 ). In a 2-compartment PK model, bodyweight was the most significant covariate for volume of distribution. There was no statistically significant difference in any PK parameter between the microdose and microtracer, nor in the area under curve ratio [14 C]1-OH-midazolam/[14 C]midazolam, showing the PK of midazolam to be linear within the range of the therapeutic and microdoses. CONCLUSION:Our data support the dose linearity of the PK of an IV [14 C]midazolam microdose in children. Hence, a [14 C]midazolam microdosing approach may be used as an alternative to a therapeutic dose of midazolam to study developmental changes in hepatic CYP3A activity in young children.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
van Groen BD,Vaes WH,Park BK,Krekels EHJ,van Duijn E,Kõrgvee LT,Maruszak W,Grynkiewicz G,Garner RC,Knibbe CAJ,Tibboel D,de Wildt SN,Turner MAdoi
10.1111/bcp.14047subject
Has Abstractpub_date
2019-10-01 00:00:00pages
2332-2340issue
10eissn
0306-5251issn
1365-2125journal_volume
85pub_type
杂志文章,多中心研究abstract:AIMS:Inherited polymorphisms of codons 16, 27, and 164 of the beta2-adrenergic receptor (B2AR) gene may result in significantly changed functions of this receptor. The aim of the present study was to investigate the frequencies of the main mutations of the B2AR gene in Turks. METHODS:A group of 104 unrelated Turkish s...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1999.00082.x
更新日期:1999-11-01 00:00:00
abstract::The classical taxanes (paclitaxel, docetaxel), the newer taxane cabazitaxel and the nanoparticle-bound nab-paclitaxel are among the most widely used anticancer drugs. Still, the optimal use and the value of pharmacological personalization of the taxanes is still controversial. We give an overview on the pharmacologica...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14678
更新日期:2020-11-28 00:00:00
abstract::A new osmotic drug delivery system (Oros) has been evaluated in multiple-dose studies in young healthy volunteers as a sustained-release vehicle for once-daily administration of oxprenolol. Two Oros systems were examined in two separate studies, one containing 170 mg oxprenolol succinate with an initial zero-order rel...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1985.tb02759.x
更新日期:1985-01-01 00:00:00
abstract::The single oral dose pharmacokinetics of carbamazepine-10, 11-epoxide (CBZ-E) were investigated in six normal volunteers during a control session and during concurrent treatment with valpromide (VPM) (300 mg twice daily for 8 days). VPM caused a prolongation of the CBZ-E half-life from 6.4 +/- 1.4 to 20.5 +/- 6.3 h an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03354.x
更新日期:1988-05-01 00:00:00
abstract::1. Twenty-two patients with moderately severe essential hypertension were treated for a period of 12 months with guanfacine (BS 100-141), a new centrally-acting antihypertensive agent. A twice daily schedule was followed and the dose range of guanfacine was 1-8 mg daily. 2. In twenty patients satisfactory blood pressu...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1980.tb04906.x
更新日期:1980-01-01 00:00:00
abstract::1 The absorption of effervescent aspirin was studied in normal volunteers of both sexes under varied conditions of activity in both fasting and non-fasting states. 2 Moderate activity resulted in no significant changes in absorption compared with that at rest. 3 In non-fasting subjects the absorption was reduced but t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1974.tb00222.x
更新日期:1974-04-01 00:00:00
abstract:AIM:To develop a semi-mechanistic model, based on glutathione depletion and predict a previously identified intra-individual reduction in busulfan clearance to aid in more precise dosing. METHODS:Busulfan concentration data, measured as part of regular care for allogeneic hematopoietic cell transplantation (HCT) patie...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14256
更新日期:2020-08-01 00:00:00
abstract::1 A total of three hundred and nineteen new chemical entities (NCEs) were investigated in man for the first time between 1964 and 1985 by seven UK-owned pharmaceutical companies. The majority (96.2%), were self-originated by the UK company or one of its overseas subsidiaries. 2 There was an increase in the number of N...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03318.x
更新日期:1988-03-01 00:00:00
abstract:AIM:In short-term studies, hormonal contraceptives (HC) have been suggested to induce a rise in blood pressure (BP) and urinary albumin excretion (UAE), while the effect of HC in renal function (GFR) is still under debate. Data on long-term and withdrawal effects of HC use on these outcomes are, however, not available....
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02747.x
更新日期:2007-02-01 00:00:00
abstract:AIM:To evaluate a context-learning pharmacotherapy programme for approximately 750 2nd, 3rd and 4th year preclinical medical students with respect to mastering cognitive pharmacotherapeutic skills, i.e. choosing a (drug) treatment and determining patient information. METHODS:The context-learning pharmacotherapy progra...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02742.x
更新日期:2006-12-01 00:00:00
abstract::The effects of the proton pump inhibitor lansoprazole on the bioavailability of a low-dose oral contraceptive (OC), containing 0.03 mg ethinyloestradiol (EE) and 0.15 mg levonorgestrel (LNG), were investigated. Twenty-four healthy females (aged 19-35 years; weight 60.6 +/- 7.1 kg) participated in a multiple-dose, plac...
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.tb04370.x
更新日期:1994-10-01 00:00:00
abstract::1. Using human mononuclear leucocytes as target cells, we have investigated the bioactivation of dapsone (DDS) to a cytotoxic metabolite in the presence of microsomes from nine human livers. Values for NADPH dependent toxicity ranged from 8.8-27% (15.8 +/- 5.9%) and were similar to those for microsomes from control mi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb03517.x
更新日期:1989-10-01 00:00:00
abstract:AIMS:Navoximod (GDC-0919, NLG-919) is a small molecule inhibitor of indoleamine-2,3-dioxygenase 1 (IDO1), developed to treat the acquired immune tolerance associated with cancer. The primary objectives of this study were to assess navoximod's absolute bioavailability (aBA), determine the mass balance and routes of elim...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13961
更新日期:2019-08-01 00:00:00
abstract::The metabolism of [3H]ethinyloestradiol (EE2) was investigated in six male subjects who had been phenotyped with respect to sparteine metabolism (three metabolizers and three non-metabolizers). Urinary metabolite profiles of EE2 were virtually identical. Following enzyme hydrolysis of sulphate and glucuronide conjugat...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02511.x
更新日期:1984-10-01 00:00:00
abstract::Adverse drug reactions come at a considerable cost on society. Social media are a potentially invaluable reservoir of information for pharmacovigilance, yet their true value remains to be fully understood. In order to realize the benefits social media holds, a number of technical, regulatory and ethical challenges rem...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12717
更新日期:2015-10-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:The dominant health economic units upon which new treatment funding decisions are made are the incremental cost per life year gained (LYG) or the cost per quality-adjusted life year (QALY) gained. Neither of these units modifies the amount of health gained, by the amount of heal...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2007.02996.x
更新日期:2008-02-01 00:00:00
abstract:AIMS:This study aimed to develop a population pharmacokinetic model for quantitative evaluation of the influence of genetic variants in metabolic enzymes and transporters on lamotrigine pharmacokinetics while taking into account the influence of various clinical, biochemical and demographic factors. METHODS:We include...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.12984
更新日期:2016-08-01 00:00:00
abstract:AIMS:Glucocorticoids suppress the release of tumour necrosis factor-alpha (TNF-alpha) by macrophages in vitro and cause monocytopaenia in vivo. These actions may contribute to anti-inflammatory and immunosuppressant effects. We therefore examined relationships between prednisolone concentration, suppression of monocyte...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1997.00586.x
更新日期:1997-04-01 00:00:00
abstract:AIMS:Our study aimed to evaluate the impacts of the cytochrome P450 (CYP) 2B6-G516T and CYP2D6 genetic polymorphisms on pharmacokinetic and clinical parameters in patients receiving methadone maintenance treatment. METHODS:Opioid PhArmacoLogy (OPAL) was a clinical survey of the sociodemographic characteristics, histor...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/bcp.13936
更新日期:2019-07-01 00:00:00
abstract::Eight psoriatic patients were treated with etretinate (50 mg daily) for 6 weeks. Skin chamber exudates from involved and uninvolved skin were assayed for arachidonic acid, 12-HETE, PGE2 and for neutrophil chemokinetic activity co-chromatographing with leukotriene B4, before and at weekly intervals during therapy. Pre-...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02499.x
更新日期:1984-10-01 00:00:00
abstract:AIMS:In man a neurokinin-1 (NK1) receptor antagonist has previously been shown to be ineffective in the prevention of motion-induced nausea. The antiemetic efficacy of NK1 receptor antagonists against chemotherapy-induced emesis is, however, enhanced when combined with a 5-HT3 receptor antagonist. Hence the efficacy of...
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.1365-2125.2000.00221.x
更新日期:2000-07-01 00:00:00
abstract::1. The effects of salmeterol hydroxynaphthoate (50 micrograms, 8.3 x 10(-8) M) and salbutamol (200 micrograms, 3.5 x 10(-7) M) on sGaw were compared in a double-blind, placebo-controlled, randomised study in 10 normal subjects. 2. SGaw increased by 29% (14-43) (mean (CI)), 5 min after salmeterol and by 35% (19-51) at ...
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.1365-2125.1992.tb04015.x
更新日期:1992-02-01 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::1 From an understanding of the biological fate and hypotensive effect of debrisoquine (D) we have assessed the relative importance of true drug resistance, inappropriately low dosage and non-compliance as causes of apparent resistance to treatment with this drug. 2 Among 37 hypertensive patients prescribed D, eleven (...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1980.tb01072.x
更新日期:1980-04-01 00:00:00
abstract:AIM:Propylene glycol (PG) is often applied as an excipient in drug formulations. As these formulations may also be used in neonates, the aim of this study was to characterize the pharmacokinetics of propylene glycol, co-administered intravenously with paracetamol (800 mg PG/1000 mg paracetamol) or phenobarbital (700 mg...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04312.x
更新日期:2013-01-01 00:00:00
abstract::1 The disposition of prazosin following oral and intravenous administration has been studied in seven young and seven elderly men, all of whom were in good health and living independently in the community. 2 The elimination half-life (min) of prazosin was 123 +/- 19.4 (s.d.) in the young and 194 +/- 36 in the elderly ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01234.x
更新日期:1981-09-01 00:00:00
abstract:AIMS:Venlafaxine may increase the risk of arrhythmia in certain patients. We sought to characterize the cardiovascular effects of venlafaxine overdose in adults. METHODS:A retrospective casenote review of patients admitted to the Royal Infirmary of Edinburgh between January 2000 and June 2006. Haemodynamic and electro...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2007.02849.x
更新日期:2007-08-01 00:00:00
abstract:AIMS:Graft spasm may develop during coronary artery bypass grafting and reversal of spasm is still challenging. The purpose of this study was to investigate the in vitro vascular relaxant properties of AJ-2615 in human internal mammary artery (IMA). METHODS:We studied 264 IMA rings taken from 65 patients undergoing co...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.0306-5251.2001.01444.x
更新日期:2001-09-01 00:00:00
abstract::1 Healthy volunteers received single doses of temazepam 30 mg in conventional gelatin capsules, suppositories or in solution. They experienced marked sedation and sleepiness. The onset of sleepiness was prompt after the administration of the solution; this latter showed the fastest absorption and gave the highest peak...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb00452.x
更新日期:1979-01-01 00:00:00
abstract::In six healthy subjects a 250 g steak significantly increased the systemic clearance of indocyanine green. During a steady-state infusion of propranolol there was a rapid decrease (mean 35%) in blood propranolol concentrations within 5 min of feeding and levels were reduced for 30 min before gradually returning toward...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb01516.x
更新日期:1983-03-01 00:00:00