Abstract:
AIMS:Health Canada has developed a pathway to approve drugs that have limited efficacy and safety data, the Notice of Compliance with conditions (NOC/c) policy. Increased safety reporting is required for these drugs but there has not been any systematic review of their post-market safety. This study compares safety warnings for NOC/c drugs with drugs with a priority and a standard review. METHODS:A list of drugs approved between January 1 1998 and March 31 2013 was developed and serious safety warnings for these drugs were identified. Drugs were put into one of three groups based on the way that they were approved. Kaplan-Meier curves were generated to examine the likelihood of NOC/c drugs receiving a serious safety warning compared with drugs with a priority and a standard review. The time spent in the review process for each of the groups was also measured. RESULTS:Compared with drugs with a priority review, NOC/c drugs were not more likely to receive a serious safety warning (P = 0.5940) but were more likely than drugs with a standard review (P = 0.0113). NOC/c drugs spent less time in the review process compared with drugs with a standard review. CONCLUSIONS:Possible reasons for the increase likelihood of a serious safety warning are the limited knowledge of the safety of NOC/c drugs when they are approved and the length of time that they spend in the review process. Health Canada should consider spending longer reviewing these drugs and monitor their post-market safety more closely.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Lexchin Jdoi
10.1111/bcp.12552subject
Has Abstractpub_date
2015-05-01 00:00:00pages
847-59issue
5eissn
0306-5251issn
1365-2125journal_volume
79pub_type
杂志文章abstract::1 The effect of acebutolol, a relatively selective beta-adrenoceptor blocking drug and propranolol, a non-selective one, on the hypoglycaemic action of glibenclamide after an oral glucose load has been investigated in a group of maturity-onset diabetic patients. 2 Glibenclamide significantly reduced the blood glucose ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb01412.x
更新日期:1982-04-01 00:00:00
abstract:AIMS:Ward physicians hold key positions in the course of efforts to reduce drug expenditures in hospitals. This study evaluated the knowledge of German hospital physicians with respect to the daily therapeutic costs of 21 frequently used drugs. METHODS:A questionnaire survey was carried out among 168 ward physicians f...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2001.01336.x
更新日期:2001-04-01 00:00:00
abstract:AIMS:Carbamazepine (CBZ) is an inducer of cytochrome P450 enzymes, which have been implicated in many drug interactions. However, for immunosuppressant and anti-HIV drugs, whose main site of action is the lymphocyte, induction of P-glycoprotein (Pgp) may also be important. In this study, we have investigated whether CB...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02587.x
更新日期:2006-08-01 00:00:00
abstract:AIM:To assess the relative contribution of intestinal and hepatic CYP3A inhibition to the interaction between the prototypic CYP3A substrate midazolam and clarithromycin in the elderly. METHODS:On day 1, 16 volunteers (eight male, eight female) aged 65-75 years weighing 59-112 kg received simultaneous doses of midazol...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.2007.02970.x
更新日期:2008-01-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:* The interindividual variability of the pharmacokinetic parameters of cilostazol is relatively large. * Cilostazol undergoes extensive hepatic metabolism via the P450 enzymes, primarily CYP3A and, to a lesser extent, CYP2C19. * Indeed, <1% of the administered dose of cilostazol...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03558.x
更新日期:2010-01-01 00:00:00
abstract:AIMS:Clozapine (CLZ), an atypical neuroleptic with a high risk of causing agranulocytosis, is metabolized in the liver to desmethylclozapine (DCLZ) and clozapine N-oxide (CLZ-NO). This study investigated the involvement of different CYP isoforms in the formation of these two metabolites. METHODS:Human liver microsomal...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1997.t01-1-00605.x
更新日期:1997-11-01 00:00:00
abstract:AIMS:To predict the drug interactions of amiodarone and other drugs, the inhibitory effects and inactivation potential for human cytochrome P450 (CYP) enzymes by amiodarone and its N-dealkylated metabolite, desethylamiodarone were examined. METHODS:The inhibition or inactivation potency of amiodarone and desethylamiod...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2000.00134.x
更新日期:2000-03-01 00:00:00
abstract:AIMS:Recently, an apparent protective effect of statins against upper gastrointestinal bleeding (UGB) was postulated in a post hoc analysis of a randomized trial. We aimed to evaluate the effect of statin use on acute nonvariceal UGB alone or in combinations with low-dose aspirin and other antithrombotic drugs. METHOD...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03362.x
更新日期:2009-04-01 00:00:00
abstract::1 The anticholinergic effects of atropine and two antihistamines (terfenadine and mequitazine) were investigated vs placebo in a double-blind study. 2 Salivary secretion, basal pupil diameter, pilocarpine (0.25%) induced miosis and heart rate were determined in eight healthy volunteers, seven male and one female, aged...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1988.tb03278.x
更新日期:1988-01-01 00:00:00
abstract:AIMS:Roux-en-Y gastric bypass (RYGB) alters the anatomical structure of the gastrointestinal tract, which can result in alterations in drug disposition. The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II - fenofibrate (bil...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.13054
更新日期:2016-11-01 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::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:AIMS:To investigate the pharmacokinetics of enterally administered cisapride suspension in young infants being treated for gastro-oesophageal reflux disease. METHODS:Plasma cisapride concentrations in 49 subjects (weight: 825-5010 g; n=108 samples, median two per patient; concentration: 14.8-170 ng ml-1 ) were fitted ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1999.00068.x
更新日期:1999-11-01 00:00:00
abstract::The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken to date with these o...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12557
更新日期:2015-05-01 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::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:AIM:To construct a population pharmacokinetic model for methadone enantiomers in the setting of methadone maintenance treatment for opioid dependence. METHODS:A population pharmacokinetic model was developed using P-Pharm software for rac-, (R)- and (S)-methadone using data (8-13 plasma samples per subject) obtained 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.1365-2125.2004.02079.x
更新日期:2004-06-01 00:00:00
abstract:AIMS:To investigate uptake of fluconazole into the interstitial fluid of human subcutaneous tissue using the microdialysis and suction blister techniques. METHODS:A sterile microdialysis probe (CMA/60) was inserted subcutaneously into the upper arm of five healthy volunteers following an overnight fast. Blisters were ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01930.x
更新日期:2003-11-01 00:00:00
abstract:AIMS:To study reporting of hypoglycaemia in angiotensin receptor blocker (ARB) users, and to investigate the possibility of confounding. METHODS:The French pharmacovigilance database was examined for an association between hypoglycaemia and ARBs or other drugs using reports notified between 1996 and 2005. This associa...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2008.03176.x
更新日期:2008-07-01 00:00:00
abstract::1. Spectral analyses of blood pressure and heart rate oscillations are increasingly used to assess the influences of diseases and drugs on the autonomic nervous system. Such influences can only be interpreted in view of the spontaneous variability of these oscillations. We therefore studied the reproducibility of powe...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1994.tb04333.x
更新日期:1994-08-01 00:00:00
abstract::1. The effect of nomifensine on the uptake of 5-hydroxytryptamine (5-HT) and dopamine (DA) into human platelet-rich plasma has been studied. 2. A significant inhibition of DA uptake was observed at nomifensine 10(-6) M. 3. 5-HT uptake was significantly inhibited only at nomifensine 10(-4) M or more. 4. These results a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1977.tb05745.x
更新日期:1977-01-01 00:00:00
abstract::1. Ten healthy subjects received two treatments: a single 1 g oral dose of nalidixic acid (NA) followed 1 h later by either an infinitesimal dilution of the drug (NA 7CH) or by succussed water which served as placebo. The study was repeated 18 months later in 10 different subjects. 2. A further 10 healthy subjects rec...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1991.tb05610.x
更新日期:1991-07-01 00:00:00
abstract:AIM:To investigate the association between risk of lupus and exposure to selected drugs implicated in risk of lupus in a number of case reports. METHODS:In this matched nested case-control study we utilized primary care data from the UK General Practice Research Database recorded between 1987 and 2001. Cases with at l...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03733.x
更新日期:2010-10-01 00:00:00
abstract:AIM:Our aim was to compare the practicability of six different potentially inappropriate medication (PIM) criteria in geriatric outpatients with polypharmacy. METHODS:We analysed baseline data from the Medication Safety Review Clinic in Taiwanese Elders (MSRC-Taiwan) study. The prevalence and correlates of PIMs were d...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04010.x
更新日期:2011-09-01 00:00:00
abstract:AIMS:To determine the paediatric licensing status in the USA, UK, Australia and New Zealand of the 79 medicines granted paediatric exclusivity in the USA, and to assess the importance of those medicines to paediatric practice. METHODS:The medicines granted a patent extension in the USA as of 10 November 2003 were iden...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2005.02327.x
更新日期:2005-06-01 00:00:00
abstract:AIMS:Kisangani is an area with intense malaria transmission and sulfadoxine-pyrimethamine resistance. Alternative antimalaria prophylaxis medication and protocols are needed, particularly with pregnant individuals. In this study, we compare the tolerance and effectiveness of mefloquine regimen as a split dose with a me...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14720
更新日期:2021-01-04 00:00:00
abstract:AIM:To use non-linear mixed effects modelling and simulation techniques to predict whether PF-04878691, a toll-like receptor 7 (TLR7) agonist, would produce sufficient antiviral efficacy while maintaining an acceptable side effect profile in a 'proof of concept' (POC) study in chronic hepatitis C (HCV) patients. METHO...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04047.x
更新日期:2012-01-01 00:00:00
abstract:AIMS:To describe the pharmacokinetic-pharmacodynamic (PK-PD) characteristics of the direct thrombin inhibitor dabigatran in hip replacement patients by assessing coagulation parameters activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT), interindividual variability and factors affecting PD respo...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02667.x
更新日期:2006-11-01 00:00:00
abstract::The in vitro conversion of enalapril (MK421) to enalaprilic acid (MK422) in human autopsy tissues was examined. MK422 was measured by radioimmunoassay. Human cadaver liver was the only tissue in which significant conversion was demonstrated. The esterase activity was stable after post mortem. Autopsy liver tissues fro...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02699.x
更新日期:1985-05-01 00:00:00
abstract:AIMS:To determine the frequency with which the selective serotonin re-uptake inhibitor (SSRI) antidepressants are used as add-on therapy to the tricyclic antidepressants (TCA) rather than as replacement therapy. METHODS:The data analysed were profiles of prescription records by date of supply to the patient. From with...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2001.01319.x
更新日期:2001-01-01 00:00:00