Abstract：
:We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly influenced our qualitative and quantitative understanding of a number of physiological and pharmacological phenomena. According to the Law of Mass Action, the velocity of a chemical reaction depends on the concentrations of the reactants. At equilibrium the concentrations of the chemicals involved bear a constant relation to each other, described by the equilibrium constant, K. The Law of Mass Action is relevant to various physiological and pharmacological concepts, including concentration-effect curves, dose-response curves, and ligand-receptor binding curves, all of which are important in describing the pharmacological actions of medications, the Langmuir adsorption isotherm, which describes the binding of medications to proteins, activation curves for transmembrane ion transport, enzyme inhibition and the Henderson-Hasselbalch equation, which describes the relation between pH, as a measure of acidity and the concentrations of the contributory acids and bases. Guldberg and Waage recognized the importance of dynamic equilibrium, while others failed to do so. Their ideas, over 150 years old, are embedded in and still relevant to clinical pharmacology. Here we explain the ideas and in a subsequent paper show how they are relevant to understanding adverse drug reactions.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Ferner RE,Aronson JKdoi
10.1111/bcp.12721subject
Has Abstractpub_date
2016-01-01 00:00:00pages
52-5issue
1eissn
0306-5251issn
1365-2125journal_volume
81pub_type
传,历史文章,杂志文章,评审abstract：:1 Twelve-week courses of oxprenolol and methyldopa were administered in a randomised, double-blind cross over study to ten insulin dependent hypertensive diabetics. 2 Prior to treatment, and at the end of each period of drug administration, fasting levels of high density lipoprotein, triglycerides, free fatty acids 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.1365-2125.1982.tb01360.x
更新日期：1982-02-01 00:00:00
abstract：:Nine young and 12 elderly healthy volunteers received nisoldipine 10 mg once a day for 7 days. Plasma nisoldipine concentrations were measured on Day 1 and on Day 7. Higher plasma drug concentrations were observed in the elderly group than in the young group with the values for AUC being approximately doubled in the e...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb05547.x
更新日期：1991-03-01 00:00:00
abstract：:1. The effect of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations was investigated in healthy volunteers in two separate studies, using a randomized cross-over design with two phases. 2. A single dose of magnesium hydroxide (850 mg) or water only (150 ml) was given immediately after...
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.tb03884.x
更新日期：1991-08-01 00:00:00
abstract：:1. The pharmacokinetics of streptokinase (SK) and anistreplase in conventional dosage regimens of 1.5 x 10(6) i.u. of SK infused over 60 min and 30 units of anistreplase over 5 min were studied in 24 consecutive patients presenting with acute myocardial infarction, using a functional bioassay to assess concentrations....
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1991.tb05502.x
更新日期：1991-02-01 00:00:00
abstract：:It is recognised that randomised controlled trials are not feasible for capturing rare adverse events. There is an increasing trend towards observational research methodologies using large population-based health databases. These databases offer more scope for adequate sample sizes, allowing for comprehensive patient ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12474
更新日期：2015-10-01 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：:The elimination of the cardioselective beta-adrenoceptor antagonist atenolol has been studied in 35 neonates by measuring drug concentration in cord blood and in blood obtained at 24 h by heel stab. Elimination rate was assessed by calculating the slopes of lines joining these two concentration points. The slopes had ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1983.tb02237.x
更新日期：1983-12-01 00:00:00
abstract：:1 Ten consecutive patients with hypertriglyceridaemia who adhered to a low carbohydrate diet without complete control of serum triglycerides were started on chenodeoxycholic acid 750 mg daily and followed monthly for 6 months. Nine of these patients were then followed for a further month on placebo capsules and therea...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1978.tb01632.x
更新日期：1978-03-01 00:00:00
abstract：AIMS:Whereas cortical EEG effects of benzodiazepines are well characterized, information about benzodiazepine effects in other areas of the central nervous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the auditory pathway in si...
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.1365-2125.2000.00104.x
更新日期：2000-01-01 00:00:00
abstract：:The effect of liver cirrhosis on plasma clearance and metabolite profile of i.v. administered antipyrine was studied in 23 patients with alcoholic liver cirrhosis (age 37-70 years) and 17 healthy subjects (age 28-55 years). Liver volume was also measured and was found to be larger in patients than in controls, mean va...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02533.x
更新日期：1984-11-01 00:00:00
abstract：:1. Azole antifungal agents such as ketoconazole act by inhibiting cytochrome P-450 mediated sterol synthesis in the fungal cell membrane and thus have the potential to interfere with mammalian steroidogenesis. Fluconazole is a novel orally-effective antifungal triazole which has been reported to have more specific eff...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1989.tb03449.x
更新日期：1989-06-01 00:00:00
abstract：:1. The new intravenous bisphosphonate drug aminohydroxypropylidine bisphosphonate (APD) is effective in treating the hypercalcaemia of malignant disease, but the optimum dose regimen is not yet established. We have treated twenty-seven patients with malignant hypercalcaemia (corrected calcium greater than 3.00 mmol l-...
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.tb05426.x
更新日期：1989-09-01 00:00:00
abstract：AIMS:To investigate the driving forces behind increasing utilization of cardiovascular drugs. METHODS:Using register data, all Danish residents as of 1 January 1996 were followed until 2006. Cohort members were censored at death or emigration. Cardiovascular drug utilization on the individual level was traced, applyin...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1111/j.1365-2125.2008.03282.x
更新日期：2008-12-01 00:00:00
abstract：AIM:To evaluate cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) reported in a prescription event monitoring study of Yasmin, an oral contraceptive. METHODS:Reports of DVT/PE and events suggestive of DVT/PE were followed up by questionnaire. RESULTS:Thirteen cases (DVT five; PE eight), each with possib...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2005.02373.x
更新日期：2005-07-01 00:00:00
abstract：:The importance of number of tablets for patient compliance was investigated in 160 patients with mild-moderate essential hypertension treated with a beta-adrenoceptor blocker and a thiazide diuretic. Mean BP at entry 146 +/- 16/92 +/- 8 mm Hg. All patients were given pindolol 10 mg and clopamide 5 mg in one combinatio...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1984.tb02388.x
更新日期：1984-05-01 00:00:00
abstract：:The airway and cardiovascular effects of intravenous neurokinin A (NKA) and substance P (SP) were compared in six normal subjects. Both SP and NKA increased skin temperature (SkT) and heart rate (HR), but SP was more potent than NKA by factors of 6 and 20 respectively. No change in systolic blood pressure (BP) occurre...
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.1365-2125.1988.tb03302.x
更新日期：1988-02-01 00:00:00
abstract：AIM:The aim was to investigate the population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome. METHODS:Non-linear mixed effects modelling was performed on samples collected during a randomized controlled trial. Samples were collected from children who were receiving 2.5 mg kg(-1) l...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12607
更新日期：2015-08-01 00:00:00
abstract：:The pharmacokinetics of single and co-administered didanosine and stavudine were evaluated in 10 HIV-seropositive subjects in an open, within subject design in which each subject received each of three treatments. Single doses of didanosine 100 mg were alternated randomly with single doses of stavudine 40 mg on days 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.1365-2125.1994.tb04374.x
更新日期：1994-11-01 00:00:00
abstract：AIMS:To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development. METHODS:Part A: open-label, randomized, 3-period crossover assessing coadm...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13925
更新日期：2019-07-01 00:00:00
abstract：:The pharmacokinetics of four sustained-release formulations of theophylline have been examined after single doses (Nuelin SA, Phyllocontin, Slo-phyllin and Theo-Dur) and at steady-state (Phyllocontin, Theo-Dur) in six healthy adult volunteers, selected because they all eliminated theophylline rapidly after an intraven...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb05116.x
更新日期：1985-12-01 00:00:00
abstract：:1. The pharmacokinetics of proguanil were evaluated in patients with acute P. falciparum malaria receiving concomitantly proguanil hydrochloride and atovaquone. The population consisted of 203 Blacks, 112 Orientals and 55 Malays; 274 males and 96 females. Of the 370 patients, 114 and 256 patients were classified as 'p...
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.tb00114.x
更新日期：1996-11-01 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:This study assessed the effects of the CYP3A inhibitors lopinavir/ritonavir (LPV/r) on the steady-state pharmacokinetics (PK) of aplaviroc (APL), a CYP3A4 substrate, in healthy subjects. METHODS:In Part 1, APL PK was determined in eight subjects who received a single oral 50-mg APL test dose with/without a single...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02661.x
更新日期：2006-09-01 00:00:00
abstract：INTRODUCTION:Irrational medicine use is a global crisis, but incidences are proportionately higher in low and middle-income countries like Sierra Leone. This study explores the structure, functions, and challenges of Drug and Therapeutics Committees (DTC) an intervention towards irrational medicines use recently pilote...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.14716
更新日期：2021-01-04 00:00:00
abstract：:The effects of ranitidine on the pharmacokinetics of metoprolol were examined in two studies. In the first study, pharmacokinetics of single doses of metoprolol were examined in six subjects before, during and after ranitidine administration for 1 week. Peak concentrations of metoprolol were increased on ranitidine bu...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb02634.x
更新日期：1985-02-01 00:00:00
abstract：:1 Benzodiazepines are regarded as pure anxiolytics, and their value in the treatment of depression is controversial. Nevertheless, symptoms of anxiety and depression coexist in patients with endogenous or neurotic depression, and clinical trials indicate that depressed patients respond better to a benzodiazepine-tricy...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1981.tb01835.x
更新日期：1981-01-01 00:00:00
abstract：:Ouabain inhibits endothelium-dependent vascular relaxation in vitro, but has not been studied in this regard in vivo. We have therefore measured blood flow responses to carbachol, bradykinin and sodium nitroprusside (endothelium-dependent and endothelium-independent vasodilators) infused into the brachial artery with ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：AIMS:To study the potential drug interaction between cimetidine and caffeine in a group of children who received cimetidine for gastritis. METHODS:The caffeine breath test was carried out prior to the administration of cimetidine and after 2-3 weeks therapy. The children (n = 1) received 300-800 mg cimetidine daily (1...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.1365-2125.1997.00589.x
更新日期：1997-05-01 00:00:00
abstract：AIMS:To compare the onset and duration of action of the new antihistamine levocetirizine with that of the second-generation antihistamine fexofenadine using the Vienna Challenge Chamber (VCC). The latter is an environment where subjects can be exposed to specific aeroallergens in controlled and reproducible conditions ...
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.1365-2125.2005.02377.x
更新日期：2005-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Develop a translational assay of Transient Receptor Potential Ankyrin 1 (TRPA1) activity for use as a preclinical and clinical biomarker. EXPERIMENTAL APPROACH:Allyl isothiocyanate (AITC), capsaicin or citric acid were applied to ears of wildtype and Trpa1-knock out (Trpa1 KO) rats, and changes ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14370
更新日期：2021-01-01 00:00:00
