Abstract:
AIMS:5-Fluorouracil (5-FU) is widely used in combination chemotherapy, and literature suggests pharmacokinetic-guided dosing to improve clinical efficacy and reduce toxicity. This study aimed to determine the pharmacokinetic exposure of both 5-FU and its metabolite, 5,6-dihydrofluorouracil (DHFU), in patients with gastrointestinal malignancy and to establish a simplified strategy to assist in therapeutic drug management for dose optimization. METHODS:This was a prospective, observational study, performed in 27 patients diagnosed with gastrointestinal malignancy who were prescribed 5-FU. Multiple samples were collected per patient over the slow bolus (15-20 min) and continuous infusion period (over 44 h) in doses 1 and 3, and the concentrations of 5-FU and DHFU were measured. RESULTS:A higher proportion of patients had exposures within the therapeutic range in dose 3 (50%) as compared to dose 1 (37.5%) with 5-FU. There was an association between delayed time to maximum concentration of DHFU and a high maximum concentration of 5-FU. A limited sampling strategy was developed with 4 samples, 2 during the bolus period and 2 during the continuous period (at 18 h and the end of infusion), which accurately predicted the total area under the curve of 5-FU. CONCLUSION:Using body surface area-based dosing with 5-FU, 50-60% of patients were outside of the therapeutic range. In the absence of genotype testing, measurement of the metabolite DHFU could be a phenotypical measure of dihydropyrimidine dehydrogenase enzyme activity. A limited sampling strategy was developed in patients who were prescribed a combination regimen of slow bolus, followed by a 44-hour continuous infusion of 5-FU to assist in the therapeutic drug management of patients.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Jacob J,Mathew SK,Chacko RT,Aruldhas BW,Singh A,Prabha R,Mathew BSdoi
10.1111/bcp.14444subject
Has Abstractpub_date
2020-06-27 00:00:00eissn
0306-5251issn
1365-2125pub_type
杂志文章abstract:AIM:To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables. METHODS:Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outco...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04208.x
更新日期:2012-08-01 00:00:00
abstract:AIMS:Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyper-responsiveness, which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levoc...
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.1365-2125.2004.02110.x
更新日期:2004-07-01 00:00:00
abstract:AIMS:To investigate the relationships between pretreatment folate concentrations, MTX pharmacokinetics and acute toxicities following high dose methotrexate (HD MTX) therapy. METHODS:MTX and its major extracellular metabolite 7-OH-MTX were measured in eight serum samples per HD MTX cycle in 65 consecutive osteosarcoma...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04054.x
更新日期:2012-01-01 00:00:00
abstract::1. The N-acetylation of dapsone (DDS) was studied in 182 unrelated healthy Japanese subjects. The frequency of slow acetylators determined using the plasma monoacetyldapsone (MADDS) to DDS ratio (MADDS/DDS, slow acetylators less than 0.30 and rapid acetylators greater than 0.35) at 3 h after an oral dose of DDS (100 m...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03333.x
更新日期:1988-04-01 00:00:00
abstract::The renal response to a challenge of maximal water diuresis has been studied in seven subjects pretreated over 48 h with either placebo, probenecid, indomethacin or piroxicam. Probenecid did not alter the excretion of water and sodium chloride when compared with placebo responses, but increased both phosphate and urat...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1988.tb03355.x
更新日期:1988-05-01 00:00:00
abstract::A double-blind controlled study comparing the effects of intravenous Diazemuls (0.15 mg kg-1) with midazolam (0.07 mg kg-1) in patients with normal liver function and with cirrhosis and portal hypertension is described. The clinical effect of the two drugs was assessed by serial tests of psychomotor function before an...
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.tb02952.x
更新日期:1986-12-01 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:AIMS:Prescribing errors are common and inadequate preparation of prescribers appears to contribute. A junior doctor-led prescribing tutorial programme has been developed for Edinburgh final year medical students to increase exposure to common prescribing tasks. The aim of this study was to assess the impact of these tu...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12147
更新日期:2014-01-01 00:00:00
abstract::Analysis of human horizontal saccadic eye movements can provide measurements of central nervous system depression and stimulation. Effects on saccadic eye movements have been observed in normal volunteers with barbiturates, benzodiazepines, opiates and related compounds, carbamazepine, amphetamine and ethanol. A suite...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02584.x
更新日期:1984-01-01 00:00:00
abstract:AIM:Sunitinib is an oral tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Because of the large interpatient pharmacokinetic variability and established exposure-response and exposure-toxicity relationships in clinical trial patients, therapeut...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14332
更新日期:2020-05-01 00:00:00
abstract::The degrees of interactions between the H2-receptor antagonists, cimetidine and ranitidine, and several beta-adrenoceptor blockers were investigated in healthy volunteers following 7 days of oral monotherapy with penbutolol, propranolol, metoprolol, pindolol and atenolol, and after co-administration with each of the H...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02428.x
更新日期:1984-01-01 00:00:00
abstract::1. The metabolic oxidation of debrisoquine (DB) was studied in 89 non-related Cuna Amerindian subjects. 2. Means and standard deviations for urinary recoveries of the intact drug and its 4-hydroxy metabolite (4-HD) were: %DB: 6.8 +/- 4.5; %4-HD: 16.0 +/- 9.1; %sum: 22.8 +/- 12.0. The log10 metabolic ratios for DB (LMR...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03776.x
更新日期:1990-08-01 00:00:00
abstract::Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03681.x
更新日期:2010-09-01 00:00:00
abstract::1. The pharmacokinetics of recombinant erythropoietin, r-Epo, were evaluated after intravenous and subcutaneous administration of 50 u kg-1 to six healthy male volunteers. 2. The calculated mean values (+/- s.d.) for volume of distribution at steady state and clearance after an i.v. dose were 76 (+/- 33) ml kg-1 and 1...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb03692.x
更新日期:1990-06-01 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. 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::A method is described for the simultaneous determination of the carboxylic acid and N-acetyl-derivatives of primaquine, in plasma and urine. After oral administration of 45 mg primaquine, to five healthy volunteers, absorption was rapid, with peak primaquine levels of 153.3 +/- 23.5 ng/ml at 3 +/- 1 h, followed by an ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02369.x
更新日期:1984-04-01 00:00:00
abstract::Highly active antiretroviral therapy is recommended for HIV-infected pregnant women to prevent mother-to-child transmission. The specific physiological background induced by pregnancy leads to significant changes in maternal pharmacokinetics, suggesting potential variability in plasma concentrations of antiretrovirals...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2008.03220.x
更新日期:2008-08-01 00:00:00
abstract:AIMS:Inflammation reduces hepatic clearance of many drugs with unknown therapeutic consequences. This study was carried out to examine the effect of rheumatoid arthritis (RA) on the pharmacokinetics and pharmacodynamics of verapamil. METHODS:Eight RA patients were age- and sex-matched with eight healthy volunteers. Th...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.2000.00314.x
更新日期:2000-12-01 00:00:00
abstract::This study investigated the effects of placebo, 1 mg, 3 mg, 10 mg and 30 mg ritanserin and 10 mg diazepam on human sleep. Twelve normal volunteers participated in this randomized, double-blind, placebo-controlled cross-over sleep study. A clear dose-response relationship was found for ritanserin with higher doses evok...
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.tb05514.x
更新日期:1991-02-01 00:00:00
abstract::1. The pharmacokinetics of didanosine, trimethoprim, and sulphamethoxazole were evaluated in ten HIV seropositive asymptomatic patients as single agents and upon coadministration of single doses. 2. Using a randomized, balanced incomplete block crossover study with at least a 1-week washout period between successive t...
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.1365-2125.1996.tb00184.x
更新日期:1996-03-01 00:00:00
abstract::The effects of delta-9-tetrahydrocannabinol (0.5 and 1 mg i.v.) on gastric emptying of liquid were investigated in seven normal volunteers and compared with placebo. Despite significant change in pulse rate and psychological parameters consistent with cannabis activity there was no significant effect on the pattern of...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1983.tb01561.x
更新日期:1983-06-01 00:00:00
abstract::1 The disposition in urine of debrisoquine and its hydroxylated metabolites has been studied in subjects of the 'extensive metabolizer' (EM; n = 5) and 'poor metabolizer' (PM; n = 5) phenotypes. The 4-hydroxylation of debrisoquine by PM subjects following a 10 mg oral dose was capacity-limited and displayed significan...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb01528.x
更新日期:1983-04-01 00:00:00
abstract:AIM:To investigate the effect of sepsis upon the volume of distribution (Vd) of gentamicin in neonates. METHODS:A retrospective chart review was conducted of neonates admitted to Dunedin Hospital who had gentamicin concentrations performed between 1st January 2000 and 30th October 2003. Data from 277 neonates, includi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2005.02260.x
更新日期:2005-01-01 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
abstract::Little is known about the administration of direct-acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, serious...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14221
更新日期:2020-08-01 00:00:00
abstract:AIM:To evaluate the efficacy of scopolamine administered transdermally for the treatment of drooling in severely disabled patients. METHODS:A prospective, randomized, double-blind, crossover, placebo-controlled clinical trial was designed. The study group consisted of 30 handicapped patients with persistent drooling. ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2010.03659.x
更新日期:2010-06-01 00:00:00
abstract::1 Data from a comprehensive drug surveillance programme are analysed to provide details of procainamide use and toxicity in medical wards of teaching hospitals in five countries. 2 Out of a total of 488 recipients 9.2% had one or more adverse effect attributed to the drug; common effects being arrhythmias, gastro-inte...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1977.tb00777.x
更新日期:1977-10-01 00:00:00
abstract::Ipratropium bromide (0.5 mg) and fenoterol (2 mg) produced equivalent peak bronchodilatation between 1 and 2 h after administration to eight patients with chronic partially reversible airways obstruction. The duration of action compared with saline was 6 h for ipratropium and 4 h for fenoterol. Both drugs in combinati...
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.tb04946.x
更新日期:1982-07-01 00:00:00
abstract:AIM:Characterization of the biliary disposition of GSK1325756, using a non-invasive bile sampling technique and spectrometric analyses, to inform the major routes of metabolic elimination and to enable an assessment of victim drug interaction risk. METHOD:Sixteen healthy, elderly subjects underwent non-invasive bile c...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04352.x
更新日期:2013-02-01 00:00:00