Abstract：
:1. The aim of the present study was to perform an in vivo estimation of the Michaelis-Menten constants of the major metabolic pathways of paracetamol (APAP). 2. A two-occasion, single-dose cross-over trial was performed using 60 and 90 mg/kg doses of APAP in healthy patients undergoing third molar dental extraction. Plasma samples were collected over 24 h and urine was collected for 8 h after dosing. Twenty patients were enrolled in the study and complete data for plasma and urine were available for both doses for 13 volunteers who were included in the analysis; seven of the volunteers were men, the median age (range) was 22 years (19-31) and the median weight (range) was 68 kg (50-86). 3. The mean (95% CI) k(m) for APAP glucuronidation was 6.89 mmol/L (3.57-10.22) and the V(max) was 0.97 mmol/h per kg (0.65-1.28). The k(m) for APAP sulphation was 0.097 mmol/L (0.041-0.152) and the V(max) was 0.011 mmol/h per kg (0.009-0.013). For the combined excretion of APAP-cysteine and APAP-mercapturate, the k(m) was 0.303 mmol/L (0.131-0.475) and the V(max) was 0.004 mmol/h per kg (0.002-0.005). 4. The estimates for in vivo Michaelis-Menten constants for APAP glucuronidation and sulphation were in the order of those reported previously using in vitro methods.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Reith D,Medlicott NJ,Kumara De Silva R,Yang L,Hickling J,Zacharias Mdoi
10.1111/j.1440-1681.2008.05029.xsubject
Has Abstractpub_date
2009-01-01 00:00:00pages
35-42issue
1eissn
0305-1870issn
1440-1681pii
CEP5029journal_volume
36pub_type
杂志文章abstract：:1. Anoxic perfusion of the isolated rat heart releases noradrenaline in the absence of sympathetic nerve fibre stimulation. 2. Anoxic noradrenaline release is enhanced by reducing the extracellular Na+ concentration, consistent with the proposal that such release occurs by carrier-mediated efflux. 3. Release is also e...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1991.tb01375.x
更新日期：1991-01-01 00:00:00
abstract：:1. In infants, promethazine has been implicated in the pathogenesis of sleep apnoea, apparent life threatening events (ALTE) and the Sudden Infant Death syndrome (SIDS). The aim of the present study was to investigate, in a neonatal animal, the effects of a commonly used promethazine-containing medication on airway pr...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2001.03483.x
更新日期：2001-07-01 00:00:00
abstract：:1. Motoneurons (MN) shape motor patterns by transforming inputs into action potential output. This transformation, excitability, is determined by an interaction between synaptic inputs and intrinsic membrane properties. Excitability is not static, but changes over multiple time scales. The purpose of the present paper...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1681.2000.03202.x
更新日期：2000-01-01 00:00:00
abstract：:The kidney has a unique environment that results in relatively low tissue oxygen tension (Po2). However, recent studies have shown that renal hypoxia is more severe during hypertension and may reflect changes in the way O2 is used. The present review summarizes studies that explore the relationship between renal oxyge...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2006.04478.x
更新日期：2006-10-01 00:00:00
abstract：:1. Pressor responsiveness to angiotensin II (AII) and phenylephrine (PHE) was measured before and after 5 days of ACTH (1 mg i.m. daily) in six normal men maintained on low sodium diet (15 mmol daily). 2. ACTH caused a significant increase in systolic blood pressure of 9 mmHg. 3. There was no change in pressor respons...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1987.tb00382.x
更新日期：1987-03-01 00:00:00
abstract：:1. The most usual form of chronic hypoxia in humans is the intermittent hypoxia resulting from obstructive sleep apnoea (OSA). The OSA syndrome is a highly prevalent sleep breathing disorder that is considered an independent risk factor for hypertension and cardiovascular diseases. Endothelial dysfunction, oxidative s...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2009.05213.x
更新日期：2009-12-01 00:00:00
abstract：:1. The role of the arterial and cardiac baroreceptors on the arginine vasopressin (AVP) and plasma renin activity (PRA) responses to haemorrhage was studied in conscious rabbits. They were bled at a rate of approximately 3% of their blood volume (BV)/min, both when the autonomic nervous system (ANS) was intact and dur...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1992.tb00412.x
更新日期：1992-11-01 00:00:00
abstract：:Acute kidney injury (AKI) occurs in 5% of hospitalized patients and in 50% of sepsis patients with acute renal dysfunction. However, there have been no safe and effective therapeutic strategies. The hypoxia condition is closely related to renal injury and function under AKI. As hypoxia-inducible factor 1α (HIF-1α) is ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12947
更新日期：2018-10-01 00:00:00
abstract：:1. Amino acid neurotransmitters are critical for controlling the activity of most central neurons, including sympathetic preganglionic neurons (SPN), the spinal cord neurons involved in controlling blood pressure and other autonomic functions. 2. In studies reviewed here, SPN were identified either by retrograde traci...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1681.2002.03664.x
更新日期：2002-05-01 00:00:00
abstract：:1. Angiotensin (Ang) II plays a major role in vascular remodelling. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in the tissue remodelling processes. The aim of the present study was to investigate whether AngII modulates TIMP-2 expression in rat aortic smooth muscle cells in vivo....
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2007.04573.x
更新日期：2007-03-01 00:00:00
abstract：:The effector mechanisms responsible for the bradycardia evoked by bilateral lesions of the brainstem coinciding with the A1 catecholamine cells were analyzed in four groups of rabbits. Sham or lesion operations were carried out in animals with intact cardiac effectors, with cardiac sympathetic block induced by propran...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1984.tb00251.x
更新日期：1984-03-01 00:00:00
abstract：:This study explored the effects and mechanisms of dopamine D1 receptors (DR1) activation on the apoptosis of osteosarcoma cells (OS732).The DR1 agonist SKF-38393 decreased the viability of OS732 cells and increased their rate of apoptosis, whereas the DR1 antagonist SCH-23390 abolished the effects of SKF-38393. In OS7...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 信件
doi：10.1111/1440-1681.12814
更新日期：2017-11-01 00:00:00
abstract：:1. The aim of the present study was to determine the brain sites mediating aspects of respiratory and cardiovascular control in adult humans using non-invasive functional magnetic resonance (fMRI) procedures, thereby avoiding the spatial and temporal sampling limitations associated with classic neural assessment techn...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1440-1681.1998.tb02240.x
更新日期：1998-06-01 00:00:00
abstract：:1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm bir...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2001.03552.x
更新日期：2001-11-01 00:00:00
abstract：:1. The role of arginine vasopressin (AVP) was examined in adrenocorticotrophin (ACTH)-induced hypertension in Sprague-Dawley rats using the non-peptide AVP V1a receptor antagonist OPC 21268. 2. In an acute study, six rats were pretreated with ACTH for 11 days and direct arterial blood pressure (4 h), plasma osmolality...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1046/j.1440-1681.2000.03350.x
更新日期：2000-11-01 00:00:00
abstract：:1. The endothelin (ET) system and NADPH oxidase play important roles in the regulation of cardiovascular function, as well as in the pathogenesis of hypertension and other cardiovascular diseases. 2. Endothelins activate NADPH oxidases and thereby increase superoxide production, resulting in oxidative stress and cardi...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2007.04830.x
更新日期：2008-01-01 00:00:00
abstract：:1. In the [(13)C]-octanoic acid breath test, the time versus pulmonary [(13)CO(2)] excretion rate curve is analysed using mathematical curve-fitting techniques to calculate gastric emptying parameters. Thus, the goodness-of-fit highly influences the accuracy of the breath test. However, a double-peaked [(13)CO(2)] exc...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1440-1681.2005.04235.x
更新日期：2005-07-01 00:00:00
abstract：:1. The aim of the present study was to assess the bioequivalence of two cefadroxil products, namely Ultracef (a reference product) in the form of a 500 mg capsule (produced by Bristol-Myers Squibb Laboratories, Princeton, NJ, USA) and Roxil (a test product) in the form of a 500 mg capsule (produced by Tabuk Pharmaceut...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1440-1681.2004.04012.x
更新日期：2004-07-01 00:00:00
abstract：:1. 125I-351A, a tyrosyl derivative of the angiotensin converting enzyme (ACE) inhibitor lisinopril, was used as a radioligand, and radioinhibitor binding and displacement assays have been established. 2. The in vitro potency of a range of ACE inhibitors against rat ACE was determined using the radioinhibitor binding d...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1988.tb01053.x
更新日期：1988-02-01 00:00:00
abstract：:1. The influence of the intact kidney on blood pressure, extracellular fluid volume (ECF, ferrocyanide space) and ECF volume distribution was studied in rats 60 days after constriction of the contralateral renal artery. 2. Renal artery constriction increased both blood pressure and ECF levels. The rise of both variabl...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1979.tb00033.x
更新日期：1979-09-01 00:00:00
abstract：:1. Asthma and chronic obstructive pulmonary disease (COPD) are chronic airway diseases characterized by airflow obstruction. The beta(2)-adrenoceptor mediates bronchodilatation in response to exogenous and endogenous beta-adrenoceptor agonists. 2. Single nucleotide polymorphisms in the beta(2)-adrenoceptor gene (ADRB2...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/j.1440-1681.2007.04731.x
更新日期：2007-10-01 00:00:00
abstract：:1. Rapid ventricular rate (VR) and rhythm irregularity during atrial fibrillation (AF) impair cardiac performance. Although digoxin has been widely used in patients with AF, its efficacy for the control of VR and rhythm irregularity is unsatisfactory. Whether low-dose amiodarone is more effective remains unclear. 2. W...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1440-1681.2001.03454.x
更新日期：2001-05-01 00:00:00
abstract：:Cardiotoxin (CTX) III, a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. In the present study, we investigated the mechanisms underlying the anticancer activity of CTX III in human leukaemia (HL-60 cells). Cardiotoxin III activated the en...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2008.04968.x
更新日期：2008-09-01 00:00:00
abstract：:Cardiac output and rhythm depend on the release and the take-up of calcium from the sarcoplasmic reticulum (SR). Excessive diastolic calcium leak from the SR due to dysfunctional calcium release channels (RyR2) contributes to the formation of delayed after-depolarizations, which underlie the fatal arrhythmias that occ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1111/1440-1681.12669
更新日期：2017-01-01 00:00:00
abstract：:1. Activation of bulbospinal neurons projecting from the C1 area of the rostral ventrolateral medulla evokes a pressor response. The nature of the neurotransmitters involved in mediating this response at spinal cord level has not been established. 2. Amino acid antagonists were introduced into the spinal subarachnoid ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1988.tb01056.x
更新日期：1988-02-01 00:00:00
abstract：:1. The influence of the passive force on the contraction and endothelium-dependent relaxation in aortae of normotensive Wistar Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP) were compared. 2. Force changes of endothelium-intact and -removed preparations were measured isometrically by a force...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1996.tb02765.x
更新日期：1996-06-01 00:00:00
abstract：:1. Metformin is one of the most commonly used drugs for the treatment of Type 2 diabetes. Accumulating evidence suggests that metformin also has cardioprotective effects. In the present study, we investigated the cardioprotective effects of metformin and the mechanisms involved. 2. A rat model of chronic heart failure...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.2010.05470.x
更新日期：2011-02-01 00:00:00
abstract：:Hepatic fibrosis is an outcome of chronic liver injury. Angiotensin II (ANG II) may play a role in the pathogenesis of hepatic fibrosis. Certain drugs such as ACE inhibitors, ANG II antagonists, and even statins could interfere with the renin angiotensin system and modulate its deleterious effects. This study was carr...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/1440-1681.12446
更新日期：2015-09-01 00:00:00
abstract：:1. Neurotensin is released from the intestine into the portal circulation and to exert a systemic effect it must traverse the liver intact. 2. The role of the liver in neurotensin clearance was examined using the isolated perfused rat liver preparation. Two concentrations of neurotensin were used to determine the extr...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章
doi：10.1111/j.1440-1681.1987.tb01870.x
更新日期：1987-10-01 00:00:00
abstract：:1. The present report documents evidence suggesting that endothelin (ET) is a mediator and modulator of post-ganglionic sympathetic neuronal development. 2. Endothelin is produced by post-ganglionic neurons and by cells adjacent to these neurons. 3. Post-ganglionic sympathetic neurons express functional receptors for ...
journal_title：Clinical and experimental pharmacology & physiology
pub_type： 杂志文章,评审
doi：10.1046/j.1440-1681.1999.03179.x
更新日期：1999-12-01 00:00:00
