Abstract:
:The binding of disopyramide (DP) and mono-N-dealkyldisopyramide (MND) was measured by equilibrium dialysis in spiked whole blood (10 mumol l-1 DP or MND) from 50 patients having a serum concentration of alpha 1-acid glycoprotein (AAG) ranging from 0.40 to 3.14 g l-1, as well as in whole blood from five healthy subjects, spiked with different concentrations of AAG ranging from 0.61 to 3.33 g l-1. The binding ratio (moles bound divided by moles unbound) in all samples increased from 1.0 to 8.0 for DP and 0.6 to 3.3 for MND with increasing AAG concentrations. The binding varied according to the AAG concentrations both in patients and healthy subjects. Similarly total and free plasma concentrations of DP and MND were also measured. With increasing AAG concentrations the total concentrations measured increased from 9.0 to 15.9 mumol l-1 for DP and from 6.8 to 11.8 mumol l-1 for MND whereas the free concentrations decreased from 3.8 to 0.5 mumol l-1 for DP and from 5.0 to 2.0 mumol l-1 for MND. With increasing AAG concentrations the whole blood/plasma concentration ratio decreased from 1.11 and 1.47 to 0.63 and 0.85 for DP and MND respectively. The ratio between their concentration in cells and the unbound concentration in plasma, however, was constant over the whole AAG concentration range. The mean ratios for all samples were 3.0 and 3.1 for DP and MND respectively, indicating that both compounds are bound or distributed to the blood cells. The distribution of the drugs in whole blood changed according to increasing AAG concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Bredesen JE,Kierulf Pdoi
10.1111/j.1365-2125.1986.tb02888.xsubject
Has Abstractpub_date
1986-09-01 00:00:00pages
281-6issue
3eissn
0306-5251issn
1365-2125journal_volume
22pub_type
杂志文章abstract::Serum free fractions of nifedipine, verapamil and some of their metabolites were measured in patients with ischaemic heart disease receiving single oral dose and chronic monotherapy and were compared with those obtained in vitro. The percentages of unbound nifedipine and verapamil in vitro (concentration range 50-200 ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb05438.x
更新日期:1989-09-01 00:00:00
abstract:AIMS:To individualize treatment, phenytoin doses are adjusted based on free concentrations, either measured or calculated from total concentrations. As a mechanistic protein binding model may more accurately reflect the protein binding of phenytoin than the empirical Winter-Tozer equation that is routinely used for cal...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14053
更新日期:2019-10-01 00:00:00
abstract:AIM:Pharmacokinetics of small molecule kinase inhibitors (KIs) used in cancer treatment may alter with increasing age, but results are conflicting. This study aims to compare exposure to KIs between older and younger patients (≥70 and <70 years) in clinical practice. METHODS:KI plasma concentrations of routinely treat...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13725
更新日期:2018-12-01 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:A systematic review of the literature published in English over 10 years was undertaken in order to describe the use of electronic healthcare data in the identification of potential adverse drug reactions (ADRs) in children. METHODS:MEDLINE and EMBASE were searched using MESH headings and text words. Titles, keyw...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12645
更新日期:2015-10-01 00:00:00
abstract::The acute peripheral vascular and diuretic effects of intravenous frusemide 10 mg and 20 mg were compared with those of bumetanide 250 micrograms and 500 micrograms in a group of 10 salt depleted volunteers. Significant reductions in forearm blood flow (FBF) were observed after frusemide 10 mg (-0.77 ml 100 ml-1 min-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.1365-2125.1986.tb05207.x
更新日期:1986-04-01 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::Exposure-response (ER) analysis has emerged as an important tool to interpret QT data from thorough QT (TQT) studies and allows the prediction of effects in the targeted patient population. Recently, ER analysis has also been applied to data from early clinical pharmacology studies, such as single and multiple ascendi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12068
更新日期:2013-11-01 00:00:00
abstract::1. The effects of a single oral dose of enalapril 10 mg on serum ACE activity and blood pressure in relation to the ACE genotype were studied in 27 healthy men, n = 9 each of genotype DD, ID and II, in a parallel group study design. 2. Before treatment serum ACE activity differed significantly between the genotypes, w...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1995.tb04419.x
更新日期:1995-02-01 00:00:00
abstract::Six human volunteers were each given single oral doses of aspirin (ASA) ranging from 300-1,500 mg. The unchanged ASA excreted in the urine was proportional to dose and urinary pH. The mean percent (+/- s.d.) of dose excreted was 1.9 +/- 0.67. The clearance for ASA was 1.42 +/- 0.28 1/h. The rate of in vitro hydrolysis...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb02030.x
更新日期:1982-10-01 00:00:00
abstract::The single oral dose pharmacokinetics of carbamazepine-10, 11-epoxide (CBZ-E) were investigated in six normal volunteers during a control session and during concurrent treatment with valpromide (VPM) (300 mg twice daily for 8 days). VPM caused a prolongation of the CBZ-E half-life from 6.4 +/- 1.4 to 20.5 +/- 6.3 h an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03354.x
更新日期:1988-05-01 00:00:00
abstract:AIMS:Flavonoids may affect platelet function by several mechanisms, including antagonism of TxA(2) receptors (TP). These TP are present in many tissues and modulate different signalling cascades. We explored whether flavonoids affect platelet TP signalling, and if they bind to TP expressed in other cell types. METHODS...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2007.02881.x
更新日期:2007-08-01 00:00:00
abstract::1 The new converting enzyme inhibitor RHC 3659 was tested in 15 male volunteers. The study consisted of two parts: first, the ability of a single oral dose (5, 10, 20, 40 or 80 mg) to inhibit the pressor response to exogenous angiotensin I was tested with blood pressure and heart rate monitored continuously through an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01327.x
更新日期:1981-12-01 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: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
abstract::1 Analgesic nephropathy is part of the analgesic syndrome which has gastrointestinal, haematological, cardiovascular, psychological and psychiatric, and pregnancy and gonadal manifestations; premature ageing may also be a feature. 2 Analgesic nephropathy is a form of renal disease characterized by renal papillary necr...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1980.tb01824.x
更新日期:1980-10-01 00:00:00
abstract::1. Preliminary results are reported from a long-term study aimed at recording the concentrations of serum lipids and lipoproteins at 6, 12 and 24 months of treatment with pindolol in young/middle-aged males with moderate hypertension. 2. Seventy-three patients have been recruited, of whom 47 have completed 6 months tr...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03272.x
更新日期:1987-01-01 00:00:00
abstract:AIMS:This study compares physicians' recall of the claims of benefits on cardiovascular disease and diabetes made by pharmaceutical sales representatives for drugs approved on the basis of a surrogate outcome, i.e., an off-label claim, compared with those approved on the basis of a serious morbidity or mortality (clini...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13360
更新日期:2017-11-01 00:00:00
abstract::1 Mianserin does not affect the uptake of biogenic amines into rat brain, in contrast to tricyclic antidepressants which block amine uptake. 2 Mianserin increases the turnover of noradrenaline (NA) in rat brain after acute or chronic administration, whereas tricyclic antidepressants reduce turnover of NA and 5-hydroxy...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1978-01-01 00:00:00
abstract::A method is described for the simultaneous determination of amodiaquine (AQ) and desethylamodiaquine (AQm) in plasma, urine, whole blood and packed red cells. After oral administration of AQ (600 mg) to seven healthy subjects, absorption of AQ was rapid, reaching peak concentrations in plasma, whole blood, and packed ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03002.x
更新日期:1987-01-01 00:00:00
abstract::The safe use of Chinese materia medica (CMM) and products in traditional Chinese medicine (TCM) practice conventionally relies on correct pharmacognostic identification, good agricultural and manufacturing practices based on pharmacopoeia standards and rational/correct CMM combinations with TCM-guided clinical prescri...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12598
更新日期:2015-10-01 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::1 Fourteen hypertensive patients were studied by intra-arterial BP monitoring to quantify the effects of standardized physiological stresses: Valsalva manoeuvre, isometric, treadmill and bicycle exercise, and 60 degree tilting before and after labetalol treatment. 2 The dose of labetalol ranged from 100--600 mg three ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract:AIM:Amiselimod (MT-1303) is a selective sphingosine 1-phosphate 1 (S1P1 ) receptor modulator which is currently being developed for the treatment of various autoimmune diseases. Unlike some other S1P receptor modulators, amiselimod seemed to show a favourable cardiac safety profile in preclinical, phase I and II studie...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13203
更新日期:2017-05-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients. :The role of genetic factors that determine the marked interindividual variability in glucose-lowering efficacy of rosiglitazone in Chinese patients is not known. The current st...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2008.03145.x
更新日期:2008-06-01 00:00:00
abstract:AIMS:Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and probenecid at renal and nonrenal sites. METHODS:A randomized, two-way crossover stud...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2009.03564.x
更新日期:2010-02-01 00:00:00
abstract:AIMS:6-mercaptopurine (6-MP) is used in the treatment of childhood acute lymphoblastic leukaemia (ALL). Its red blood cell (RBC) metabolite concentrations (6-thioguanine [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) are related to drug response. We investigated the impact of non-genetic covariates and pharma...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03867.x
更新日期:2011-04-01 00:00:00
abstract::1 The effect of an intravenous bolus of labetalol (0.6-1.6 mg/kg body weight) on central and peripheral haemodynamics was studied in nine subjects with essential hypertension and in eleven subjects with chronic renal disease and hypertension. 2 The BP reduction amounting to 20/13 mmHg was entirely due to the lowering ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb04764.x
更新日期:1979-04-01 00:00:00
abstract:AIMS:To develop a population pharmacokinetic model for lopinavir in combination with ritonavir, in which the interaction between both drugs was characterized, and in which relationships between patient characteristics and pharmacokinetics were identified. METHODS:The pharmacokinetics of lopinavir in combination with r...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2005.02455.x
更新日期:2005-10-01 00:00:00
abstract::1. Previous studies have demonstrated the presence of antibodies to trifluoroacetylated hepatic proteins (TFA-proteins) in sera from patients with the severe form of halothane-associated hepatitis (halothane hepatitis). The TFA-proteins are produced via cytochrome P450-mediated metabolism of halothane to the reactive ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1995.tb04560.x
更新日期:1995-10-01 00:00:00