Abstract:
AIMS:To investigate the impact of the specific red blood cell binding on the pharmacokinetics and pharmacodynamics of the nucleoside transport inhibitor draflazine after i.v. administration at various infusion rates. It was also aimed to relate the red blood cell (RBC) occupancy of draflazine to the ex vivo measured adenosine breakdown inhibition (ABI). METHODS:Draflazine was administered to healthy volunteers as a 15-min i.v. infusion of 0.25, 0.5, 1, 1.5 and 2.5 mg immediately followed by an infusion of the same dose over 1 h. Plasma and whole blood concentrations were measured up to 120 h post dose, and were related to the ex vivo measured ABI, serving as a pharmacodynamic endpoint. The capacity-limited specific binding of draflazine to the nucleoside transporter located on the erythrocytes was evaluated by a population approach. RESULTS:The estimate of the population parameter typical value (%CV) of the binding constant Kd and the maximal specific binding capacity (Bmax) was 0.385 (3.5) ng ml-1 plasma and 158 (2.1) ng ml-1 RBC, respectively. The non-specific binding was low. The specific binding to the erythrocytes was a source of non-linearity in the pharmacokinetics of draflazine. The total plasma clearance of draflazine slightly decreased with increasing doses, whereas the total clearance in whole blood increased with increasing doses. The sigmoidal Emax equation was used to relate the plasma and whole blood concentration of draflazine to the ex vivo determined ABI. In plasma, typical values (%CV) of Emax, IC50 and Hill factor were 81.4 (1.9)%, 3.76 (9.3) ng ml-1 and 1.06 (3.4), respectively. The relationship in whole blood was much steeper with population parameter typical values (%CV) of Emax, IC50 and Hill factor of 88.2 (2.0)%, 65.7 (2.8) ng ml-1 and 4.47 (5.5), respectively. The RBC occupancy of draflazine did not coincide with the ex vivo measured ABI. The observed relationship between RBC occupancy and ABI was not directly proportional but similar for all studied infusion schemes. CONCLUSIONS:The findings of this study show that the occupancy of the nucleoside transporter by draflazine should be at least 90% in order to inhibit substantially adenosine breakdown in vivo. On the basis of these findings it is suggested that a 15 min infusion of 1 mg draflazine followed by an infusion of 1 mg h-1 could be appropriate in patients undergoing a coronary artery bypass grafting.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Snoeck E,Piotrovskij V,Jacqmin P,Van Peer A,Danhof M,Ver Donck K,Woestenborghs R,Van Belle H,Van Bortel L,Van Gool R,Dupont AG,Heykants Jdoi
10.1046/j.1365-2125.1997.00593.xsubject
Has Abstractpub_date
1997-06-01 00:00:00pages
603-12issue
6eissn
0306-5251issn
1365-2125journal_volume
43pub_type
临床试验,杂志文章,随机对照试验abstract::Concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured by h.p.l.c. in plasma and cerebrospinal fluid (CSF) samples from 16 patients with cancer receiving oral (controlled-release) morphine. There was a close correlation between plasma and CSF morphine concentrations (r ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1994.tb04352.x
更新日期:1994-09-01 00:00:00
abstract::The effects of bopindolol, a new beta-adrenoceptor blocker, on the exercise tolerance of 12 in-patients, mean age 57 (5 years), with stable angina pectoris and documented coronary artery disease were evaluated. All patients received on 4 different days a single oral dose of bopindolol 0.5 mg, bopindolol 1.0 mg, bopind...
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:1991-12-01 00:00:00
abstract::1 A double-blind entry to a trial of an active non-steroidal anti-inflammatory drug, flurbiprofen against placebo was undertaken until 100 patients with classical rheumatoid arthritis had been allocated to each treatment. 2 Each patient was given a long-term supply of drug and was asked to vary their own dosage within...
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.1365-2125.1978.tb01654.x
更新日期:1978-05-01 00:00:00
abstract::A 12-week double-blind study was performed to compare the safety and efficacy of doxazosin, prazosin and placebo in 172 patients with essential hypertension. According to response, patients received doxazosin 1-16 mg once daily, prazosin 0.5-10 mg twice daily, or placebo. Mean final daily doses were doxazosin 11.3 mg ...
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.tb02856.x
更新日期:1986-01-01 00:00:00
abstract::The mydriatic response to eyedrops of the anticholinergic drug tropicamide at very low concentration (0.01%) was studied in subjects with Alzheimer's disease (AD, n = 10) and multi-infarct dementia (MID, n = 10). There was no significant difference in pupillary response between the two groups. The test is unlikely to ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1996.tb00194.x
更新日期:1996-03-01 00:00:00
abstract:AIMS:To determine whether repeated once daily administration of grapefruit juice altered the pharmacokinetics or pharmacodynamics of the calcium antagonist amlodipine. METHOD:S The effects of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral and intravenous amlodipine were assessed in 20 healthy me...
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.1365-2125.2000.00283.x
更新日期:2000-11-01 00:00:00
abstract::The effects of ranitidine on the pharmacokinetics of metoprolol were examined in two studies. In the first study, pharmacokinetics of single doses of metoprolol were examined in six subjects before, during and after ranitidine administration for 1 week. Peak concentrations of metoprolol were increased on ranitidine bu...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02634.x
更新日期:1985-02-01 00:00:00
abstract::The binding of carbamazepine and carbamazepine 10,11-epoxide to serum, albumin and alpha 1-acid glycoprotein (AAG) was determined and compared at drug concentrations ranging from 0.5 to 400 mg/l using equilibrium dialysis and liquid chromatography. The total binding of carbamazepine in serum was determined primarily b...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02496.x
更新日期:1984-10-01 00:00:00
abstract::1 Previous studies of propranolol disposition in renal failure have been conflicting. 2 Using simultaneous administration of [3H]-propranolol intravenously and unlabelled propranolol orally the principal determinants of drug distribution were calculated in normals, patients with severe renal impairment (creatinine cle...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1980.tb00511.x
更新日期:1980-12-01 00:00:00
abstract::The effect of salbutamol on bronchoconstriction induced by inhaled sodium metabisulphite has been studied in 12 atopic subjects. Salbutamol (200 micrograms, 3.5 x 10(-7) M) and matched placebo were administered by identical metered dose inhaler 15 min before a dose-response to sodium metabisulphite (1.25-100 mg ml-1) ...
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.tb03967.x
更新日期:1991-11-01 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:We performed a prospective cohort study to gain more insight into risk factors for neuropsychiatric effects of mefloquine among tourists travelling to tropical areas. METHODS:We enrolled all patients who consulted the Travel Clinic of the Havenziekenhuis & Institute for Tropical Diseases Rotterdam for mefloquine ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.02035.x
更新日期:2004-04-01 00:00:00
abstract::1 A controlled trial of charcoal haemoperfusion as an early treatment for paracetamol overdose showed no benefit. 2 The plasma clearances of paracetamol by the charcoal column were variable and disappointingly small (range 4-119 ml/minute). The cumulative amounts removed were also low, mean 1.4 g (range 0.2-5.2 g). 3 ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1974.tb00249.x
更新日期:1974-06-01 00:00:00
abstract:UNLABELLED:What is already known about this subject? The naturally occurring interlukin-1 receptor antagonist (IL-1RA) markedly protects rodents against ischaemic, excitotoxic and traumatic brain injury, suggesting it may be of therapeutic value. When administered intravenously to patients soon after stroke, IL-1RA is ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2007.03026.x
更新日期:2008-03-01 00:00:00
abstract::Both the acute blood pressure lowering and renal effects of the calcium antagonist nicardipine and those after 1 week's treatment were investigated in 10 normotensive volunteers and in 10 patients with mild to moderate essential hypertension. After 1 week of placebo, nicardipine was administered orally for 1 week (20 ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb05022.x
更新日期:1984-07-01 00:00:00
abstract:AIM:We compared the efficacy of melatonin and placebo as adjuvants in the withdrawal of patients from long term temazepam, zopiclone or zolpidem (here 'BZD') use. METHODS:A double-blind, placebo-controlled, randomized trial was conducted in a primary health care outpatient clinic. Ninety-two men or women (≥55 years) w...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12294
更新日期:2014-06-01 00:00:00
abstract:AIMS:To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS:Continuous radial pulse wave analysis, whole-body impedance cardiograp...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03434.x
更新日期:2009-07-01 00:00:00
abstract::Model-based prediction on clinical doses for cannabinoids therapy is beneficial in the clinical setting, especially for seriously ill patients with both altered pharmacokinetics and pharmacodynamic responses. The objective of this article is to review the currently available PK and/or PD models of Δ9-tetrahydrocannabi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13635
更新日期:2018-11-01 00:00:00
abstract::The effect of isotonic bicycle exercise on beta 2-adrenoceptors and cAMP production in lymphocytes was studied. The origin of the newly exposed receptors was studied by measuring radioligand binding in the presence of hydrophylic or lipophylic 'cold' ligands. During exercise beta 2-adrenoceptor density increased from ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb05487.x
更新日期:1990-01-01 00:00:00
abstract::Mirabegron is used for the treatment of symptoms associated with overactive bladder syndrome. It selectively stimulates the β3 -adrenoreceptor, which relaxes the detrusor muscle. This improves urine storage by distension of the bladder body. ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12647
更新日期:2015-10-01 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::Self-poisoning by ingestion or inhalation is common, and it is important to study its various epidemiological manifestations with clear definitions. Data on fatal self-poisonings are recorded nationally within the UK and are codified according to the International Classification of Diseases (ICD) revision relevant at ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01910.x
更新日期:2003-12-01 00:00:00
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 tool...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14360
更新日期:2020-12-01 00:00:00
abstract::1. In a double-blind, placebo-controlled, cross-over study, acute pharmacokinetic, neurophysiological and psychotropic effects of suriclone, a new cyclopyrrolone derivative, were investigated and compared with alprazolam. 2. Fifteen normal young volunteers received randomized oral single doses of placebo, 0.1, 0.2 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:10.1111/j.1365-2125.1994.tb04254.x
更新日期:1994-02-01 00:00:00
abstract::1. The pharmacokinetics, bioavailability and metabolism of nitrendipine were studied in six healthy volunteers (three females, three males) using [13C4]-nitrendipine as a biological internal standard. In the first study the drug was administered simultaneously by the i.v. [13C4] and p.o. (solution) routes and in a sec...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03214.x
更新日期:1987-11-01 00:00:00
abstract::1 A treatment group comprising 635 hypertensive men (casual SBP greater than 175 or DBP greater than 115 twice) was compared with a reference group (n = 391 men; casual SBP greater than 175 or DBP greater than 115 only at screening). All men belonged to the same population sample of 7,455 men aged 47-54 yr. 2 The two ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb04699.x
更新日期:1979-01-01 00:00:00
abstract::Pharmacological interactions in both directions between phenprocoumon and atenolol and metoprolol were investigated using a crossover trial. Co-administration of phenprocoumon did not significantly affect Cmax, tmax, t1/2,22, AUC for atenolol or metoprolol. Co-administration of metoprolol, but not atenolol, increased ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02439.x
更新日期:1984-01-01 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:AIMS:The aims of the present study were, firstly, to evaluate long-term trends in the occurrence and treatment of cardiovascular disease (CVD) risk factors and the occurrence of CVD events in children with type 1 diabetes mellitus (T1DM) and, secondly, to assess the determinants of undertreatment of CVD risk factors. ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13482
更新日期:2018-04-01 00:00:00
abstract:AIMS:In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury wo...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.02032.x
更新日期:2004-04-01 00:00:00