Abstract：
:The influence of cimetidine pretreatment on the pharmacokinetics of 5-fluorouracil (5FU) has been studied in 15 ambulant patients with carcinoma. Neither pretreatment with a single dose of cimetidine (400 mg) nor with daily treatment at 1000 mg for 1 week altered 5FU pharmacokinetics. Pretreatment with cimetidine for 4 weeks (1000 mg daily) led to increased peak plasma concentrations of 5FU and also area under the plasma concentration-time curve (AUC). The peak plasma concentration after oral 5FU was increased by 74% from 18.7 +/- 4.5 micrograms/ml (mean +/- s.e. mean) to 32.6 +/- 4.4 micrograms/ml (P less than 0.05) and AUC was increased by 72% from 528 +/- 133 micrograms/ml-1 min (mean +/- s.e. mean) to 911 +/- 152 micrograms ml-1 min (P less than 0.05). After intravenous 5FU, AUC was increased by 27% from 977 +/- 96 micrograms ml-1 min (mean +/- s.e. mean) to 1353 +/- 124 micrograms ml-1 min (P less than 0.01). Total body clearance for 5FU following intravenous administration was decreased by 28% from 987 +/- 116 ml/min (mean +/- s.e. mean) to 711 +/- 87 ml/min (P less than 0.01). The elimination half-life of 5FU was not altered by cimetidine. The basis of the interaction between 5FU and cimetidine is uncertain but probably a combination of inhibited drug metabolism and reduced liver blood flow. The therapeutic implications are considerable and additional care should be taken in patients receiving the two drugs concomitantly.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Harvey VJ,Slevin ML,Dilloway MR,Clark PI,Johnston A,Lant AFdoi
10.1111/j.1365-2125.1984.tb02484.xsubject
Has Abstractpub_date
1984-09-01 00:00:00pages
421-30issue
3eissn
0306-5251issn
1365-2125journal_volume
18pub_type
杂志文章abstract：AIMS:This study aimed to investigate possible effects of ABCB1 genotype on fluvastatin, pravastatin, lovastatin, and rosuvastatin pharmacokinetics. METHODS:In a fixed-order crossover study, 10 healthy volunteers with the ABCB1 c.1236C/C-c.2677G/G-c.3435C/C (CGC/CGC) genotype and 10 with the c.1236T/T-c.2677T/T-c.3435T...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2009.03440.x
更新日期：2009-08-01 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：: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:Although genetic, clinical and demographic factors have been shown to explain approximately half of the inter-individual variability in warfarin dose requirement in adults, less is known about causes of dose variability in children. This study aimed to identify and quantify major genetic, clinical and demographic ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12308
更新日期：2014-07-01 00:00:00
abstract：AIMS:The aim was to describe the utilization of antidiabetic agents, in terms of persistence and regimen change, in the management of a cohort of newly treated type 2 diabetes patients and to investigate associated socio-demographic and treatment factors. METHODS:A population-based retrospective cohort study was condu...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12573
更新日期：2015-06-01 00:00:00
abstract：:1 Thirty-six patients with various neurological diseases or symptoms received single intravenous doses of either cimetidine 400 mg (n = 19) or oxmetidine 200 mg (n = 17), 15 or 60 min before a diagnostic lumbar puncture. 2 In the 15 min CSF samples concentrations of cimetidine were detectable but not measurable in 5 a...
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.1365-2125.1982.tb02042.x
更新日期：1982-12-01 00:00:00
abstract：AIMS:In order to evaluate a hypothesized protective effect of the use of HMG Co-A reductase inhibitors (statins) on the development of Type 2 diabetes, we conducted a nested case-control study based on data from the UK-based General Practice Research Database (GPRD). METHODS:We identified a population of adults 30-79 ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2004.02142.x
更新日期：2004-09-01 00:00:00
abstract：AIMS:To study the delivery of 15 mg beclomethasone 17,21-dipropionate (BDP) to the distal part of the small bowel for three oral sustained-release formulations (I-III) and a reference capsule in volunteer ileostomists, and to compare these findings with the in vitro dissolution profiles. METHODS:Two groups of nine ile...
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.1365-2125.1998.00782.x
更新日期：1998-09-01 00:00:00
abstract：:This study compared the efficacy of 8 mg controlled release (CR) salbutamol tablets twice daily with standard 4 mg salbutamol tablets four times daily in patients with chronic obstructive airways disease. There was significant bronchodilation in both treatment groups as measured by standard spirometry (P less than 0.0...
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.tb03683.x
更新日期：1990-05-01 00:00:00
abstract：AIMS:Smoking is a major risk factor for developing atherosclerosis. In order to understand the vascular abnormalities observed in smokers, we investigated vascular responsiveness in cigarette smokers. METHODS:We performed two consecutive matched group comparative studies to investigate vascular responsiveness using ve...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.0306-5251.2001.01434.x
更新日期：2001-08-01 00:00:00
abstract：AIMS:The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. METHODS:The study was designed as a retrospective reanalysis of existing...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12828
更新日期：2016-04-01 00:00:00
abstract：AIM:To evaluate the resistance to oxidation of human lipoproteins after hypolipidaemic therapy. METHODS:VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a randomized, double-blind, cross-over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice daily, or...
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.1365-2125.1998.00672.x
更新日期：1998-03-01 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:To characterize the absorption kinetics and bioavailability of an inhaled hydrophilic solute deposited at various sites within the airways. METHODS:Nine healthy nonsmokers received one intravenous, one oropharyngeal and two pulmonary doses of technetium-99 m-labelled diethylene triamine pentaacetic acid ((99m)Tc-...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02835.x
更新日期：2007-06-01 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：AIMS:This study assessed the effects of the CYP3A inhibitors lopinavir/ritonavir (LPV/r) on the steady-state pharmacokinetics (PK) of aplaviroc (APL), a CYP3A4 substrate, in healthy subjects. METHODS:In Part 1, APL PK was determined in eight subjects who received a single oral 50-mg APL test dose with/without a single...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02661.x
更新日期：2006-09-01 00:00:00
abstract：:1. Mizolastine, a new benzimidazole derivative with potent selective, non-sedative H1-histamine antagonist activity was compared with terfenadine, cetirizine and loratadine using the histamine-induced wheal and flare model in healthy volunteers. 2. Study design was a five way double-blind crossover design using a sing...
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：1995-11-01 00:00:00
abstract：:Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulator of cell growth, division and survival. Many haematologic malignancies exhibit elevated or aberrant mTOR activation, supporting the launch of numerous clinical trials aimed at evaluating the potential of single agent m...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12888
更新日期：2016-11-01 00:00:00
abstract：AIMS:Adrenomedullin (ADM) is an important regulator of endothelial barrier function and vascular tone, and may represent a novel treatment target in sepsis. The non-neutralizing ADM antibody adrecizumab has shown promising results in preclinical sepsis models. In the present study, we investigated the safety, tolerabil...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13655
更新日期：2018-09-01 00:00:00
abstract：:1. The cardiovascular responses to handgrip exercise have been studied in ten patients with uncomplicated essential hypertension in a randomized crossover study of propranolol and prazosin. 2. Isometric handgrip exercise was performed with a calibrated strain gauge dynamometer at 30% of maximum voluntary contraction f...
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.1365-2125.1979.tb04720.x
更新日期：1979-10-01 00:00:00
abstract：AIMS:Previous isobolographic analysis revealed that coadministration of morphine and oxycodone produces synergistic antinociception in laboratory rodents. As both opioids can produce ventilatory depression, this study was designed to determine whether their ventilatory effects were synergistic when coadministered to he...
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.1365-2125.2005.02368.x
更新日期：2005-05-01 00:00:00
abstract：AIMS:This analysis was performed to investigate the population pharmacokinetics of clomethiazole and its effect on the natural course of sedation in acute stroke patients using a nonlinear mixed effects modelling approach. METHODS:One thousand five hundred and forty-six acute stroke patients (774 on active treatment) ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1046/j.0306-5251.2003.01850.x
更新日期：2003-08-01 00:00:00
abstract：:1 Measurements of the binding of 12-alpha-[3H]-digoxin to the membranes of intact erythrocytes, erythrocyte 86rubidium uptake and intraerythrocytic sodium concentrations have been made in the red cells of various groups of patients--those who have not received digoxin, those during the early phases of treatment, those...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1979.tb05811.x
更新日期：1979-08-01 00:00:00
abstract：:The frequency distributions of the 0-8 h urinary metabolic ratios of debrisoquine and mephenytoin were measured in 111 healthy, unrelated Sinhalese resident in Sri Lanka. Blood samples were taken from 77 of these subjects for CYP2D6 genotyping. Bimodality in the distribution of the log10 debrisoquine/4-hydroxydebrisoq...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1994.tb04384.x
更新日期：1994-11-01 00:00:00
abstract：AIMS:Angiotensin receptor blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short term effects may ha...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.12655
更新日期：2015-10-01 00:00:00
abstract：:1 The haemodynamic effects of labetalol 50 mg intravenously were studied in 13 hypertensive patients at rest in the supine and upright positions and during exercise using percutaneous right heart and brachial artery catheterization. 2 Labetalol induced immediate significant reductions in systolic and diastolic blood p...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1976-08-01 00:00:00
abstract：:1. In order to assess attitudes of patients to participation in therapeutic trials 197 patients underwent structured interviews conducted by a single observer. Of these patients 66 were previous or current participants in clinical trials (group A), 12 had declined participation in a trial (group B), and 119 had never ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：AIM:The aim was to examine patients' stated preferences to persist with medicines and to explore the influence of psychosocial and sociocognitive factors. METHODS:Community-dwelling, hypertensive patients recruited from nine European countries were invited to complete a discrete choice experiment (DCE) with attributes...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12971
更新日期：2016-08-01 00:00:00
abstract：:The absorption of the antiemetic metopimazine (MPZ) given as a single dose of (a) 40 mg microenema, (b) 40 mg orally and (c) 10 mg as a 60 min i.v. continuous infusion was investigated in six healthy volunteers. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite were measured. The bio...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.1365-2125.1996.35220.x
更新日期：1996-06-01 00:00:00
abstract：:1 The anti-hypertensive effect of labetalol given twice or three times daily was evaluated in ambulant subjects with essential hypertension by recording blood pressure directly for 24 h before and after 15 d of labetalol administration (daily dose 600-1800 mg). 2 Labetalol reduced 24 h systolic and diastolic blood pre...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1982.tb01886.x
更新日期：1982-06-01 00:00:00
