Abstract：
AIMS:The study was designed to evaluate the relative bioavailability of diclofenac in plasma, subcutaneous adipose and skeletal muscle tissue after repeated topical administration using MIKA Diclofenac Spray Gel (4%), a novel formulation, and after oral dosing using VOLTAREN 50 mg enteric coated tablets. METHODS:Diclofenac (48 mg) was administered topically three times daily for 3 days onto a defined area of the thigh of 12 healthy males. After a 14-day wash out period, subjects were orally treated with 50 mg diclofenac three times daily for 3 days. In vivo microdialysis in subcutaneous and muscle tissues was performed immediately after the final doses from both treatments on day 4, and 48 h later. Plasma samples were taken simultaneously. RESULTS:The relative bioavailability of diclofenac in subcutaneous adipose and skeletal muscle tissue was substantially higher after topical compared with oral dosing (324% and 209%, respectively) whereas relative plasma bioavailability was 50-fold lower. Plasma C(max) values were approximately 250-fold lower after topical compared with oral drug administration (i.e. median values = 4.89 ng mL(-1); 95% CI: 3.37-7.68 and 1240 ng mL(-1); 95% CI: 787-1389 ng mL(-1)). Both treatments were well tolerated. CONCLUSIONS:Owing to its favourable penetration characteristics and low systemic availability, MIKA Diclofenac Spray Gel 4% is a rational alternative to oral diclofenac formulations for the treatment of inflammatory soft tissue conditions.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Brunner M,Dehghanyar P,Seigfried B,Martin W,Menke G,Müller Mdoi
10.1111/j.1365-2125.2005.02484.xkeywords:
subject
Has Abstractpub_date
2005-11-01 00:00:00pages
573-7issue
5eissn
0306-5251issn
1365-2125pii
BCP2484journal_volume
60pub_type
杂志文章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. Oxycodone hydrochloride (0.1 mg kg-1) was given by intravenous bolus to 18 children after ophthalmic surgery. Plasma was sampled for up to 8 h. Blood pressure, heart rate, peripheral arteriolar oxygen saturation, end-tidal carbon dioxide and halothane concentrations and ventilatory rate were also recorded. 2. Mean ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1994.tb04324.x
更新日期：1994-07-01 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：AIMS:Naloxegol, a polyethylene glycol conjugated derivative of the opioid antagonist naloxone, is in clinical development for treatment of opioid-induced constipation (OIC). The aim of the study was to develop a population pharmacokinetic model describing the concentration vs. time profile of orally administered naloxe...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12756
更新日期：2016-01-01 00:00:00
abstract：AIM:The large inter-individual variability in clopidogrel response is attributed to pharmacokinetics. Although, it has been used since the late 1990s the pharmacokinetic fate of clopidogrel and its metabolites are poorly explained. The variable response to clopidogrel is believed to be multi-factorial, caused both by g...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12017
更新日期：2013-06-01 00:00:00
abstract：:The effect of charcoal-drug ratio on the antidotal efficacy of oral activated charcoal was studied in six healthy volunteers in a randomized cross-over study and compared with the adsorption capacity of activated charcoal in vitro. Aminosalicylic acid (PAS) 1 g and 5 g were ingested on an empty stomach in 30 ml of wat...
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.1365-2125.1985.tb02712.x
更新日期：1985-06-01 00:00:00
abstract：:1. Lisinopril and enalapril were administered as 2.5 mg single doses and as eight single daily 2.5 mg doses to separate groups of six patients with chronic renal failure. Patients were receiving regular haemodialysis. 2. In the absence of haemodialysis, the decline in plasma concentrations of lisinopril and enalaprila...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1988.tb05319.x
更新日期：1988-12-01 00:00:00
abstract：AIMS:To examine the hypothesis that sildenafil, a phosphodiesterase type 5 inhibitor that inhibits cGMP breakdown, could enhance nitric oxide-mediated vasodilation and reverse endothelial dysfunction in chronic smokers. METHODS:Flow-mediated dilation of the brachial artery and forearm postischemic reactive hyperemia (...
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.1365-2125.2003.01974.x
更新日期：2004-02-01 00:00:00
abstract：:1 The rate of methaqualone metabolism in women was shown to be significantly increased at the time of ovulation. 2 The apparent first order rate constants for the formation of five C-monohydroxy metabolites of methaqualone on day 15 of the menstrual cycle were approximately double that on day 1. 3 The N-oxidation of m...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1982.tb01988.x
更新日期：1982-09-01 00:00:00
abstract：:The metabolism of morphine was studied in seven fullterm neonates and five infants receiving a continuous infusion of morphine. All the patients had detectable plasma concentrations of morphine 3-glucuronide (M3G) and 10 had detectable concentrations of morphine 6-glucuronide (M6G). The mean plasma clearance of morphi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1992.tb05652.x
更新日期：1992-11-01 00:00:00
abstract：AIMS:To examine how pharmaceutical products that were first marketed between 1950 and 1980 were promoted to physicians through advertisements and briefly review advertising regulations and accuracy of the advertisements in the light of modern knowledge. METHODS:We systematically reviewed advertisements promoting drugs...
journal_title：British journal of clinical pharmacology
pub_type： 历史文章,杂志文章
doi：10.1111/bcp.13549
更新日期：2018-08-01 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：:Cefpiramide is a new parenteral cephalosporin mainly excreted in the bile. Eight patients with cholestasis and 11 healthy subjects received a single 1 g i.v. dose. Cefpiramide concentrations in plasma and urine were measured by h.p.l.c. and plasma binding was determined by ultrafiltration. Total clearance of cefpirami...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1994.tb04278.x
更新日期：1994-03-01 00:00:00
abstract：AIMS:The efficacy of activated charcoal alone, and gastric lavage followed by charcoal in reducing the absorption of diazepam, ibuprofen and citalopram was studied in healthy volunteers. METHODS:In a randomized cross-over study with three phases, nine healthy volunteers were administered single oral doses of 5 mg diaz...
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.1365-2125.1999.00995.x
更新日期：1999-08-01 00:00:00
abstract：:1. We have studied the effects of age, sex and the oral contraceptive pill on platelet fibrinogen 'receptor' density (Bmax) and affinity (Kd). 2. [125I]-fibrinogen binding to gel-filtered platelets was assessed after stimulation with adenosine 5-diphosphate (ADP) and thrombin in 60 normal subjects; 37 females and 23 m...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1992.tb03994.x
更新日期：1992-01-01 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：:The binding of carbamazepine and carbamazepine 10,11-epoxide to serum, albumin and alpha 1-acid glycoprotein (AAG) was determined and compared at drug concentrations ranging from 0.5 to 400 mg/l using equilibrium dialysis and liquid chromatography. The total binding of carbamazepine in serum was determined primarily b...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02496.x
更新日期：1984-10-01 00:00:00
abstract：:1 Cimetidine has been reported to reduce serum calcium and parathyroid hormone (PTH) levels in primary hyperparathyroidism, but some studies have reported negative findings. 2 A double-blind, controlled trial of cimetidine in this condition was, therefore, conducted. Eight patients were given cimetidine and placebo fo...
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.tb04960.x
更新日期：1982-11-01 00:00:00
abstract：:1 Seventeen men, aged 45-57 yr, with essential hypertension showed obvious and, in the standing position, dose-related reductions in blood pressure during treatment with oral labetalol with weekly dose increments. 2 Pulse rate changes were not related to dose but reduced compared with pre-treatment values. 3 No postur...
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 48 patients with chronic asthma who had been receiving treatment with beclomethasone dipropionate aerosol (BDA) at a daily dose of 400 microgram for several years, observations were made on the effect of increasing the dose to 800 microgram daily for 6 months. 2. There was subjective improvement in 37 of the 48 ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1977.tb04516.x
更新日期：1977-01-01 00:00:00
abstract：:The discovery of immune checkpoints and their role in modulating immune response have revolutionised cancer treatment in recent years. The immune checkpoints, cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 and its ligand, programmed cell death-ligand 1, have been extensively studied. Curr...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14338
更新日期：2020-09-01 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：AIMS:To study the pharmacokinetics and bioavailability of the prodrug bambuterol and its bronchodilator moiety terbutaline in healthy subjects. METHODS:Eight healthy subjects (four women) received intravenous doses of bambuterol and terbutaline. On a third occasion, they, plus another four subjects, ingested oral bamb...
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.1365-2125.1998.00695.x
更新日期：1998-05-01 00:00:00
abstract：:1. Medication errors are common in general practice and in hospitals. Both errors in the act of writing (prescription errors) and prescribing faults due to erroneous medical decisions can result in harm to patients. 2. Any step in the prescribing process can generate errors. Slips, lapses, or mistakes are sources of e...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2009.03425.x
更新日期：2009-06-01 00:00:00
abstract：:1. To assess the risk of end-stage renal disease (ESRD) associated with the regular use of three classes of non-narcotic analgesics, we performed a case-control study of 340 patients with ESRD on a haemodialysis maintenance program and 673 hospital controls. 2. The overall odds ratio estimate for non-narcotic analgesi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1990.tb03841.x
更新日期：1990-11-01 00:00:00
abstract：:1. A survey has been conducted amongst 459 members of the Clinical Section of the British Pharmacological Society to ascertain facts about the administration of drugs to healthy volunteers over the period October 1986 to September 1987. 2. A response rate of 87.1% was obtained with 114 individuals being involved in he...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb05342.x
更新日期：1989-02-01 00:00:00
abstract：BACKGROUND:Benzodiazepines and "Z drugs" are often prescribed in residents of nursing homes (NH) despite their well-known deleterious effects. We aimed to investigate if a general intervention on quality of care led to discontinuation of benzodiazepine, and to examine which NH-related factors were associated in change ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12847
更新日期：2016-04-01 00:00:00
abstract：:1. Using human mononuclear leucocytes as target cells, we have investigated the bioactivation of dapsone (DDS) to a cytotoxic metabolite in the presence of microsomes from nine human livers. Values for NADPH dependent toxicity ranged from 8.8-27% (15.8 +/- 5.9%) and were similar to those for microsomes from control mi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb03517.x
更新日期：1989-10-01 00:00:00
abstract：AIMS:Statins have been suggested to prevent haematological malignancies. Several epidemiological studies have evaluated this association, while randomized controlled trials (RCTs) on cardiovascular outcomes have provided relevant data as secondary end-points. Our aim was to examine the strength of this association thro...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,meta分析,评审
doi：10.1111/j.1365-2125.2007.02959.x
更新日期：2007-09-01 00:00:00
abstract：AIMS:To examine the feasibility of using the human iris in vivo for the assessment of the interaction between tyramine and monoamine oxidase (MAO) inhibitors. To examine the relative roles of the two forms of MAO in terminating the response to sympathomimetic amines in the iris, by comparing the effects of single oral ...
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.1365-2125.1998.00729.x
更新日期：1998-06-01 00:00:00
