Abstract:
:1. The calcineurin inhibitor cyclosporine is widely used to prevent allograft rejection after solid organ transplantation. It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics. Interindividual differences in the activity and expression of the metabolising enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp) contribute considerably to cyclosporine pharmacokinetics. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. 2. The aim of the present study was to evaluate retrospectively the effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine dose adjusted trough blood concentration during the early period after renal transplantation in Chinese patients. 3. One hundred and six renal transplant recipients in China were genotyped by polymerase chain reaction-restriction fragment length polymorphism for CYP3A4*18A, CYP3A5*3 and MDR1 C3435T. Cyclosporine whole blood levels were measured by fluorescence polarization immunoassay. Dose-adjusted trough blood concentrations (C(0)) were determined and compared among the different genotype groups. 4. The frequency of the CYP3A4*18A, CYP3A5*3 and MDR1 C3435T variant alleles were 0.005 (95% confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528 (95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete linkage disequilibrium. The median cyclosporine dose-adjusted C(0) in CYP3A5*1/*1 genotype subjects (n = 6) was 14.8 ng/mL per mg per kg (range 11.1-26.8 ng/mL per mg per kg), in CYP3A5*1/*3 patients (n = 34) it was 23.7 ng/mL per mg per kg (range 9.0-61.0 ng/mL per mg per kg) and for CYP3A5*3/*3 patients (n = 66) it was 26.4 ng/mL per mg per kg (range 9.8-85.8 ng/mL per mg per kg; P = 0.012, Kruskal-Wallis test). Accordingly, cyclosporine dose-adjusted C0 was larger in CYP3A5 non-expressors than expressors in the first week after renal transplantation. In addition, wild-type homozygotes (n = 21) for MDR1 C3435T had a slight but significantly lower dose-adjusted C0 compared with heterozygotes (n = 58): 17.7 (10.3-60.8) versus 26.4 (9.0-67.3) ng/mL per mg per kg, respectively (P = 0.014, Mann-Whitney U-test). 5. In conclusion, the present study shows that genetic polymorphisms in CYP3A5 may be responsible, in part, for the large interindividual variability of cyclosporine pharmacokinetics during the early phase after renal transplantation in Chinese patients. Patients with the CYP3A5*3 variant genotype require a low dose of cyclosporine to reach target levels compared with those with the CYP3A5*1 allele.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Hu YF,Qiu W,Liu ZQ,Zhu LJ,Liu ZQ,Tu JH,Wang D,Li Z,He J,Zhong GP,Zhou G,Zhou HHdoi
10.1111/j.1440-1681.2006.04492.xsubject
Has Abstractpub_date
2006-11-01 00:00:00pages
1093-8issue
11eissn
0305-1870issn
1440-1681pii
CEP4492journal_volume
33pub_type
杂志文章abstract::Previous studies have shown that endothelin (ET)-1 stimulates thromboxane (Tx)A(2) production and so we hypothesized that inhibiting prostanoid TP receptors would prevent the pressor and intrarenal haemodynamic response to an acute infusion of ET-1. 2. Male Sprague-Dawley rats were anaesthetized with Inactin (Sigma Ch...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04354.x
更新日期:2006-03-01 00:00:00
abstract::Rats were prepared with chronic cannulae in the carotid artery, jugular vein and urinary bladder; they were then kept 2 days to allow recovery from surgery. A steady-state continuous saline diuresis was established, then various anaesthetic agents were injected and changes in the urine flow, sodium and potassium excre...
journal_title:Clinical and experimental pharmacology & physiology
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doi:10.1111/j.1440-1681.1985.tb02311.x
更新日期:1985-03-01 00:00:00
abstract::The amino acid sequence of human renin was identified for the first time. This was determined from the nucleotide sequence of exons in the human renin gene identified in a genomic library by recombinant DNA techniques. Examination of amino acid residues involved in the enzymatic hydrolysis by human renin of the unique...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00281.x
更新日期:1984-07-01 00:00:00
abstract::The epithelial sodium channel (ENaC) has long been recognized as playing a vital role in blood pressure (BP) regulation due to its involvement in fluid balance. The genes encoding the three ENaC subunits are likewise important contributors to hypertension, both in rare monogenic diseases and in the general population....
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12124
更新日期:2013-08-01 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 neurotrophins play an important role during development to stimulate and guide axonal growth for the establishment of a correctly wired and functional neural system. Neurotrophins can also regulate adult nervous system plasticity by promoting neuronal survival and stimulating nerve regrowth following injury. 2....
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2003.03909.x
更新日期:2003-10-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13449
更新日期:2020-12-21 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1985.tb00300.x
更新日期:1985-01-01 00:00:00
abstract::1. In a controlled, randomized double-blind trial, 15 patients with essential hypertension were treated with enalapril 5-20 mg/day, or doxazosin 1-8 mg/day, during a 7 week dose titration phase. This was followed by 7 weeks of combined treatment with doxazosin and enalapril. 2. Blood was taken after a 2 week placebo r...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1992-05-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03809.x
更新日期:2003-03-01 00:00:00
abstract::1. The aim of the present study was to investigate the structural requirements for the inhibition of 6-methyl-hydroxylation of the antitumour agent 5,6-dimethyl-xanthenone-4-acetic acid (DMXAA) by acridine analogues and use a CYP1A2 homology model to provide some insight into this interaction. 2. Concentrations causin...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.0305-1870.2005.04243.x
更新日期:2005-08-01 00:00:00
abstract::1. There is controversy regarding plasma catecholamine levels in patients with hypertrophic cardiomyopathy (HCM) and few data exist on serial plasma catecholamine measurements during exercise. The present study determined whether cardiovascular and plasma catecholamine responses to exercise were altered in patients wi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1998.tb02177.x
更新日期:1998-12-01 00:00:00
abstract::The anti-acetylcholinesterase (AChEase) activity of 15 opioids, namely morphine, nalorphine, oxymorphone, naloxone, naltrexone, N-methylnaloxone, levorphanol, levallophan, dextrorphan, dextrallophan, levo-methadone, dextro-methadone, pethidine, leu-enkephalin and U-50,488H was investigated. Among the opioids, the morp...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1986.tb00330.x
更新日期:1986-02-01 00:00:00
abstract::1. Adult soft-shelled turtles were exposed to hyperosmotic and dehydration stresses. 2. Acute treatment for 0.5, 1 or 2 h with sodium chloride (3.6%, single intramuscular injection, 2 mL volume) caused depletion of pineal serotonin contents followed by elevation of norepinephrine and epinephrine levels. In addition, i...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01386.x
更新日期:1991-10-01 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::Urapidil had blocking activity on alpha 1-adrenoceptors in the rat isolated caudal artery (pA2 congruent to 7) and in the anaesthetized rat. Urapidil had no clonidine like agonistic activity on alpha 2-adrenoceptors in preparations of the guinea-pig ileum (prejunctional) or dog saphenous vein (post-junctional). Urapid...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00289.x
更新日期:1984-07-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2000.03305.x
更新日期:2000-08-01 00:00:00
abstract::Mutations of αB-crystallin (CryαB), a small heat shock protein abundantly expressed in cardiac and skeletal muscles, are known to cause desmin-related myopathies. The CryαB R120G allele has been linked to a familial desminopathy and, in transgenic mice, causes a sudden death at about 28 weeks of age. To investigate th...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.12253
更新日期:2014-08-01 00:00:00
abstract::1. Renin is highly expressed in submandibular gland (SMG) of mouse, which has two genes, Ren-1d and Ren-2d, but not at all in rat SMG. Differences in nuclear protein binding to renin promoter DNA were, therefore, explored. 2. Rat -169 to +23 renin DNA formed complexes with both mouse and rat extract, whereas a corresp...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01684.x
更新日期:1993-05-01 00:00:00
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journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1998.tb02188.x
更新日期:1998-02-01 00:00:00
abstract::1. Interactions between autacoids may play important roles in the regulation of blood flow in the foetal placenta. In order to investigate this aspect of placental haemodynamics, human normal-term placentae were perfused in vitro and the responses of the foetal vessels to various combinations of vasoactive agents were...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1998.tb02280.x
更新日期:1998-09-01 00:00:00
abstract::1. Ventilatory measurements and functional residual capacity (FRC) were recorded from anaesthetized rats and ferrets using a whole body plethysmograph. Simulation of aspects of human chronic obstructive airways disease (COAD) was attempted by making animals acutely hypoxic or hypoxic and hypercapnic by causing them to...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1987.tb02420.x
更新日期:1987-11-01 00:00:00
abstract::1. The effects of the Class I anti-arrhythmic drugs quinidine, procainamide, lidocaine, phenytoin and tocainide on mitochondrial lactate dehydrogenase activity were compared in guinea-pig heart preparations. 2. All the tested drugs inhibited the enzyme activity in a concentration-dependent fashion, exhibiting varying ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1993.tb01671.x
更新日期:1993-04-01 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
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更新日期:2004-07-01 00:00:00
abstract::The beta-receptor stimulant effects of Sm220Cl, dl-N-(1,1-dimethyl-3-phenylpropyl)-2-hydroxy-2-(3,4-dihydroxy-2-methoxyphenyl)ethylamine, and (-)-isoprenaline have been compared in isolated atrial (beta1) and tracheal (beta2) preparations from guinea-pigs and cats. 2. The compounds were also tested for their ability t...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1977.tb02672.x
更新日期:1977-07-01 00:00:00
abstract::1. In the present study, we examined whether the nuclear transcription factor (NF)-kappaB activity plays a role in the determination of sensitivity to tumour necrosis factor (TNF)-alpha or agonistic Fas antibody (Ab) in human vascular smooth muscle cells (hVSMC). 2. To inhibit agonist-induced NF-kappaB activation in h...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03817.x
更新日期:2003-03-01 00:00:00
abstract::1. Arterial baroreceptor denervation produces acute hypertension, but chronically denervated animals have an average arterial pressure that is similar to that of baroreceptor intact animals. 2. Although cardiopulmonary baroreceptors and renal compensations have been suggested to mediate the restoration of a normal ave...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1997.tb01787.x
更新日期:1997-01-01 00:00:00
abstract::1. The intravenous administration of nicergoline (5 mg) was followed by a rapid and sustained lowering of blood pressure; less rapid effects were bradycardia and an elevation of cardiac output. These delayed effects are consistent with an indirect action on the alpha-adrenoreceptors of the central nervous system. 2. F...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1980.tb00051.x
更新日期:1980-03-01 00:00:00
abstract::1. Kynurenine aminotransferase catalyzes the conversion of kynurenine to kynurenic acid, an endogenous antagonist of excitatory amino acid receptors. The kynurenic acid content and kynurenine aminotransferase activity was measured in micro-dissected regions of spontaneously hypertensive rats (SHR) and their normotensi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02460.x
更新日期:1994-11-01 00:00:00
abstract::1. Twelve treated hypertensive patients (ages 58-71 years) who had also been treated for joint disease participated in a randomized double-blind crossover placebo-controlled study to investigate the effects of indomethacin (25 mg three times daily) on blood pressure and biochemical parameters over a 6-week period. 2. ...
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.1440-1681.1981.tb00763.x
更新日期:1981-09-01 00:00:00