Abstract:
AIMS:To investigate the impact of cytochrome P450 2D6 (CYP2D6) on dose-adjusted serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol in a therapeutic drug monitoring (TDM) cohort of psychiatric patients. We also studied the functional impact of CYP2D6*41 on dose-adjusted serum concentrations in the perphenazine-treated patients. METHODS:Serum concentrations of flupentixol, haloperidol, perphenazine and zuclopenthixol from CYP-genotyped patients were extracted retrospectively from a routine TDM database in the period March 2005 to May 2019. Samples were divided into three CYP2D6 phenotype subgroups according to genotype; normal metabolizers (NMs), intermediate metabolizers (IMs) and poor metabolizers (PMs). The effect of CYP2D6 phenotype on dose-adjusted serum concentrations of the four antipsychotics was evaluated by multivariable mixed model analyses. RESULTS:Mean dose-adjusted serum concentrations of perphenazine (564 samples) were 3.9-fold and 1.6-fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .001 and P < .01). For zuclopenthixol (658 samples), mean dose-adjusted serum concentrations were about 1.5-fold and 1.3-fold higher in CYP2D6 PMs and IMs, respectively, compared with NMs (P < .01 and P < .001). CYP2D6 was of minor or no importance to haloperidol (320 samples) and flupentixol (115 samples). In our data material, the genotype CYP2D6 *1/*41 appears to have a similar impact on dose-adjusted serum concentrations of perphenazine as *1/null (null = variant allele encoding no enzyme function). CONCLUSIONS:This study shows that CYP2D6 is important for the metabolism of perphenazine and zuclopenthixol, but not for haloperidol and flupentixol. The CYP2D6*41 allele appears to have a reduced function close to nonfunctional variant alleles.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Waade RB,Solhaug V,Høiseth Gdoi
10.1111/bcp.14626subject
Has Abstractpub_date
2020-10-28 00:00:00eissn
0306-5251issn
1365-2125pub_type
杂志文章abstract:AIMS:To evaluate if rivaroxaban, an oral factor Xa (FXa) inhibitor, could modify the expression in vitro of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus. METHODS:AAA sites with intraluminal mural thrombus were obtained from six patients undergoin...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13383
更新日期:2017-12-01 00:00:00
abstract:AIMS:To assess the reproducibility of the digital pulse wave response to beta(2)-adrenoreceptor stimulation and to determine if an attenuated response to beta(2)-adrenoceptor stimulation is associated with impaired flow mediated dilatation (FMD). METHODS:Subjects (n = 20) with endothelial dysfunction (ED), were compar...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2007.03006.x
更新日期:2008-02-01 00:00:00
abstract::The pharmacokinetics of antipyrine were studied in 12 healthy volunteers and 10 patients of Kenya African origin with Hodgkin's lymphoma. The half-life of antipyrine was 12.2 +/- 1.3 h (mean + s.d.), while the apparent volume of distribution (V) was 0.67 +/- 0.11 l kg-1 (mean +/- s.d.) and the total body clearance was...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03249.x
更新日期:1987-12-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:• Terutroban is a selective TP receptor antagonist, i.e. a specific antagonist of the thromboxane A(2) and prostaglandin endoperoxide receptors, shown to improve endothelial function after a single administration in patients with coronary artery disease. WHAT THIS STUDY ADDS:• ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2010.03858.x
更新日期:2011-06-01 00:00:00
abstract::1. The effects of sodium octanoate and sodium salicylate on the rectal absorption of cefoxitin were investigated in healthy volunteers. Drug solutions were given either as a bolus or as a zero-order infusion. 2. On rectal infusion sodium octanoate and sodium salicylate both enhanced mean cefoxitin bioavailability (+/-...
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.1365-2125.1989.tb05337.x
更新日期:1989-01-01 00:00:00
abstract::1. Hydrochlorothiazide (HCT, 50-75 mg) was administered orally to seven patients with cardiac failure. 2. Plasma levels and urinary concentration of HCT were determined by GLC. 3. The gastrointestinal uptake of the diuretic in three patients was reduced to approximately half that seen in healthy controls. 4. Plasma ha...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb04646.x
更新日期:1979-06-01 00:00:00
abstract::The clinical efficacy, the bronchodilating effect and the side effects of two oral forms of terbutaline were compared in a double-blind, cross-over study involving ten patients with chronic reversible airways obstruction. The administration of plain-tablets, containing 2.5 mg terbutaline sulphate, three times daily 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.1365-2125.1986.tb05178.x
更新日期:1986-02-01 00:00:00
abstract:AIMS:The aim of this study was to investigate the impact of new insights and revised guidelines on initial and follow-up treatment with antihyperglycaemic drugs over the period 1998-2003. METHODS:The InterAction Database (IADB), which contains pharmacy dispensing data from 53 community pharmacies in the Northern and E...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02711.x
更新日期:2006-12-01 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:AIM:To investigate the effect of the P-glycoprotein inhibitor verapamil on the pharmacokinetics and pharmacodynamics of dabigatran etexilate (DE). METHOD:In this two part multiple crossover trial in 40 healthy subjects, DE 150 mg was given alone or with verapamil at different doses, duration of treatment (single vs. m...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2012.04453.x
更新日期:2013-04-01 00:00:00
abstract:AIMS:To investigate whether the drug-drug interaction between fexofenadine and ketoconazole is localized to efflux transport proteins of the small intestine, and to determine and classify the effective jejunal permeability (Peff) of fexofenadine according to the Biopharmaceutics Classification System (BCS). METHODS:Tw...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01722.x
更新日期:2003-02-01 00:00:00
abstract:AIMS:Since suspicion has been raised that administration of an oral live attenuated rotavirus vaccine may increase the risk of intussusception in young children, there has been concern about the possible effects of oral polio vaccine. The aim of the study was to evaluate the relationship between oral attenuated polio v...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2001.00090.x
更新日期:2001-10-01 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::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
abstract:AIM:We compared the pharmacokinetic (PK) profiles of co-crystal of tramadol-celecoxib (CTC) vs. each reference product (alone and in open combination) after single (first dose) and multiple dosing. METHODS:Healthy adults aged 18-50 years received, under fasted conditions, 15 twice-daily doses of the following treatmen...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13428
更新日期:2018-01-01 00:00:00
abstract:AIM:To review the literature on adverse drug reactions (ADRs) in children with respect to occurrence, seriousness, type, therapeutic group, age and gender of the child and category of reporter. METHODS:Medline and Embase databases were searched from origin and updated until February 2010. We included empirically based...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2010.03682.x
更新日期:2010-10-01 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::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:AIMS:To examine the potency of ticlopidine (TCL) as an inhibitor of cytochrome P450s (CYP450s) in vitro using human liver microsomes (HLMs) and recombinant human CYP450s. METHODS:Isoform-specific substrate probes of CYP1A2, 2C19, 2C9, 2D6, 2E1 and 3A4 were incubated in HLMs or recombinant CYPs with or without TCL. Pre...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2000.00175.x
更新日期:2000-04-01 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:AIMS:To determine whether enzyme-inducing antiseizure drugs (ASDs) affect the risk of developing chronic obstructive pulmonary disease (COPD) or lung cancer in smokers. METHODS:Cases of COPD and lung cancer and matched controls without these conditions were identified from a population of smokers with ≥1 prescription ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14501
更新日期:2020-08-01 00:00:00
abstract::1 Chronic treatment with a constant dose of hydrochlorothiazide or tienilic acid increases plasma renin activity (PRA) acutely to reach a maximum within the first week. 2 During chronic diuretic therapy from 1 month to 1 year, PRA remained elevated at a rather constant level, though this was somewhat lower than the ma...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01231.x
更新日期:1981-09-01 00:00:00
abstract::1. The absorption kinetics of orally administered strontium chloride and its reproducibility were investigated in healthy volunteers after administering strontium either under fasting conditions (study I, n = 8) or in combination with a standardized meal (study II, n = 8). Each subject received strontium orally at day...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1996.33411.x
更新日期:1996-06-01 00:00:00
abstract::Ten patients with mild to moderate hypertension were treated for 9 weeks with a tablet formulation of pinacidil. Mean supine blood pressure fell from 174/100 to 148/84 mm Hg and mean supine pulse increased by 3 beats/min. Daily dosage was 40-100 mg, given in two or three divided doses. Plasma urea increased significan...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02456.x
更新日期:1984-08-01 00:00:00
abstract:AIMS:The aims of the study were to determine the effect of advice from the Scottish Medicines Consortium (SMC) on the use of medicines within Scotland's National Health Service (NHS) and generate hypotheses that may explain differences in the impact of advice on the use of individual medicines. METHODS:A retrospective...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03826.x
更新日期:2011-02-01 00:00:00
abstract::1. The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzyme inhibitor ramipril (2.5 mg) and the extended release formulation of the dihydropyridine calcium channel antagonist felodipine (5 mg) were assessed in a double-blind, double dummy placebo controlled, randomi...
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.1365-2125.1993.tb00371.x
更新日期:1993-10-01 00:00:00
abstract:AIMS:Previously published pharmacokinetic (PK) models for sunitinib and its active metabolite SU12662 were based on a limited dataset or lacked important elements such as correlations between sunitinib and its metabolite. The current study aimed to develop an improved PK model that circumvented these limitations and to...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12550
更新日期:2015-05-01 00:00:00
abstract:AIMS:To develop a population pharmacokinetic model for mycophenolic acid (MPA) in children with idiopathic nephrotic syndrome (INS) treated with mycophenolate mofetil (MMF), identify covariates that explain variability and determine the Bayesian estimator of the area under the concentration-time curve over 12 h (AUC(0-...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/j.1365-2125.2010.03615.x
更新日期:2010-04-01 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::1. The primary aim of this study was to assess the impact of renal haemodynamics on the pharmacokinetic behaviour of ibuprofen enantiomers. Thirty-two patients and ten age-matched healthy volunteers participated in this study. These patients had at least one of the following risk factors for cardiovascular disorders: ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1995.tb04536.x
更新日期:1995-07-01 00:00:00