Abstract：
:The immunosuppressive activity of azathioprine (AZA) is unpredictable and depends on the formation of intracellular thiopurine ribonucleotides. However, the quantification of these active thiopurines presents difficult analytical problems. It has recently been postulated that plasma concentrations of 6-thiouric acid (6-TU) and 6-mercapto-purine (6-MP), metabolites of AZA, may provide more readily measurable indices of the pharmacologic activity of AZA. In order to evaluate the utility of 6-TU and 6-MP plasma concentrations in monitoring AZA therapy, we studied their pharmacokinetics in 6 renal transplant patients, and their in vitro immunosuppressive potency in a mixed lymphocyte proliferation assay. A peak plasma 6-TU concentration of 710.7 ng/ml was observed at 3.8 h after oral dosing. Good correlation was observed between the elimination t1/2 of 6-TU and serum creatinine, and between AUC over 24 h and serum creatinine. However, we did not observe a second peak in plasma 6-TU concentration that could be attributed to the degradation of active AZA metabolites. 6-MP plasma concentrations in the patients were low (mean peak concentration 36.0 ng/ml) and rapidly disappeared within 8 h. In vitro immunosuppressive activity could not be demonstrated for 6-TU over a concentration range of 1.25 ng/ml to 0.25 mg/ml. We conclude that 6-TU is pharmacologically inert and is primarily eliminated by the kidneys. Our findings currently do not support the use of plasma concentrations of 6-TU or 6-MP to monitor AZA therapy. In order to optimize AZA therapy, analytical techniques that are technically feasible and that can directly quantify the active intracellular thiopurines are being explored.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Chan GL,Erdmann GR,Gruber SA,Stock P,Chen S,Ascher NL,Canafax DMdoi
10.1007/BF00558158subject
Has Abstractpub_date
1989-01-01 00:00:00pages
265-71issue
3eissn
0031-6970issn
1432-1041journal_volume
36pub_type
杂志文章abstract：PURPOSE:Intravenous (IV) magnesium sulfate (MgSO4) is used as adjunct therapy to treat acute asthma exacerbations. Despite its clinical use, there is a limited understanding of the disposition of magnesium in children. METHODS:To explore the pharmacokinetics (PK) of IV MgSO4 in this population, we collected retrospect...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2165-3
更新日期：2017-03-01 00:00:00
abstract：:Ninety-six depressed outpatients from 5 centres were given viloxazine 200-400 mg/day. The treatment produced significant clinical improvement as evaluated by the Hamilton Rating Scale for Depression. Thirteen patients dropped-out because of possible side effects. Many untoward symptoms were described by all the patien...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00613832
更新日期：1983-01-01 00:00:00
abstract：:The clearance of chlordiazepoxide from the systemic circulation was studied in 20 subjects which included 15 patients with alcoholic hepatitis and 5 normal volunteers. The half-life for the appearance of the drug in the systemic circulation was found to increase exponentially with age (r = 0.73, P less than 0.0005) an...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00562805
更新日期：1981-03-01 00:00:00
abstract：PURPOSE:To investigate interindividual variability in response to pain treatment, we characterized postoperative patients for morphine metabolism and for COMT, OPRM1 and UGT2B7 polymorphisms. METHODS:A total of 109 patients treated with morphine were genotyped by DNA sequencing for 12 DNA polymorphisms of the COMT, OP...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-013-1523-7
更新日期：2013-09-01 00:00:00
abstract：INTRODUCTION:This study compared the characteristics of new human drugs approved by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC) in the period 2007 to 2016. METHODS:The list of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 20...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-018-2431-7
更新日期：2018-06-01 00:00:00
abstract：:Encainide is a new anti-arrhythmic drug, which is highly effective against ventricular extrasystoles, both single and coupled, in the dose range of 80--140 mg i.v. Ventricular extrasystoles were abolished in 31 out of 33 cases treated. The drug is also relatively effective against supraventricular extrasystoles, but h...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00605629
更新日期：1979-11-01 00:00:00
abstract：OBJECTIVE:Because of the risk of haemorrhagic disease of the newborn as a result of a deficit in vitamin K, it is generally agreed that newborns should receive vitamin K. However, there is no consensus concerning the route of administration, dose, number of doses, or dose frequency. METHODS:We studied patterns of vita...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050297
更新日期：1997-01-01 00:00:00
abstract：:The debrisoquine/sparteine-type polymorphism of drug oxidation and the polymorphism for acetylation are two common inherited variations in human drug metabolism. The phenotypes for hydroxylation and acetylation can be predicted be newly developed methods based on mutation-specific amplification of DNA by the polymeras...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF02220616
更新日期：1992-01-01 00:00:00
abstract：OBJECTIVE:The efficacy of beta-adrenergic blocking agents and acetylsalicylic acid in the secondary prevention of myocardial infarction has been well recognized since the beginning of the 1980s. In a previous paper, however, we reported a lower than expected use of these drugs during the period 1982 1988. In 1989 the r...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050446
更新日期：1998-05-01 00:00:00
abstract：:The diabetogenic effect of deflazacort (DF), an oxazolinic synthetic corticosteroid, was studied in 12 healthy adult subjects with a positive family history of diabetes mellitus. Three oral glucose tests (oGTT) were performed at 9.00 a.m., after a 12 h fast, following randomized administration of Placebo (PL), or Defl...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00542555
更新日期：1982-01-01 00:00:00
abstract：OBJECTIVES:To investigate whether treatment with acarbose alters the pharmacokinetics (PK) of coadministered rosiglitazone. METHODS:Sixteen healthy volunteers (24-59-years old) received a single 8-mg dose of rosiglitazone on day 1, followed by 7 days of repeat dosing with acarbose [100 mg three times daily (t.i.d.) wi...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280100275
更新日期：2001-05-01 00:00:00
abstract：:The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B(5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits u...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00542319
更新日期：1982-01-01 00:00:00
abstract：:A new device for IV admixtures has been developed in Israel, the Vialink minibag. It consists of a partly filled minibag, attached by rubber tubing to a sterile receptable into which various types of vials containing drugs can be firmly inserted. Time and motion studies were conducted to determine the time and cost as...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00194973
更新日期：1994-01-01 00:00:00
abstract：:The effects of metolazone on the protein binding of glibenclamide were studied. It was found that increasing metolazone concentrations up to 100 ng/ml had no significant effect on the protein binding of glibenclamide studied at 10 micrograms/ml. Metolazone is unlikely to cause a clinically significant increase in the ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314813
更新日期：1990-01-01 00:00:00
abstract：:There are many questions concerned with therapy and its application. Depending on the perspective of the study there can be several "populations" which, when considered individually, may give different, or even inconsistent conclusions. These populations are: the sick population, the therapist's target population, the...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314951
更新日期：1991-01-01 00:00:00
abstract：:We examined the pharmacokinetics of nifedipine after acute and sustained oral therapy and the potential haemodynamic interaction between nifedipine and sublingual nitroglycerin in nine patients with chronic stable angina. Nifedipine pharmacokinetics after a single oral dose and sustained dosing (three times daily for ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00637629
更新日期：1987-01-01 00:00:00
abstract：:Eighty patients recovering from major operations were investigated to evaluate the influence of naloxone on the analgesic and respiratory depressant properties of buprenorphine. They were randomly assigned to two groups to self-administer either buprenorphine (Group B) or a mixture of buprenorphine and naloxone (fract...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00542434
更新日期：1988-01-01 00:00:00
abstract：:Tolbutamide (1 g/70 kg) was administered as a single intravenous dose to 31 healthy, non-smoking, drug-free males between 23 and 87 years old and the total amounts of hydroxy and carboxytolbutamide excreted in 24 h were measured. There was a significant decrease in the urinary recovery of both metabolites with age. Th...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF02336696
更新日期：1990-01-01 00:00:00
abstract：OBJECTIVE:To determine the patterns of consumption in calcium channel blockers (CCB) groups in the Czech Republic between 1992 and 1999 and make a comparison with selected countries. METHODS:This was part of a drug utilization study using WHO methodology [Anatomical Therapeutic Chemical classification/defined daily do...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-002-0489-7
更新日期：2002-10-01 00:00:00
abstract：:Factors influencing the disposition of clotiazepam in man were evaluated in a series of pharmacokinetic studies in healthy volunteers given a single 5 mg dose. Old age caused an increased volume of distribution of clotiazepam in women, and its clearance tended to be reduced in elderly men. Use of oral contraceptives, ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00546709
更新日期：1984-01-01 00:00:00
abstract：:In the 3rd paragraph and 2nd line of the Conclusion section the correct sentence should be: It is now important to encourage policy and decision makers to facilitate and accommodate future linkage of data. ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,已发布勘误
doi：10.1007/s00228-017-2358-4
更新日期：2017-11-01 00:00:00
abstract：:The pharmacokinetics of intravenous enprofylline has been studied in 8 children with asthma. The mean plasma half-life of enprofylline (1.0 h) was considerably shorter than that previously reported in adults. The half-life determined from log urine excretion rate data was identical to the plasma half-life, so urine ex...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00637683
更新日期：1987-01-01 00:00:00
abstract：:Glycerol 50 g infused i.v. over 2 to 6 h is widely used to treat cerebral oedema in patients with acute stroke. Its transit through the blood-cerebrospinal fluid barrier in subjects with uninflamed meninges has now been examined. In 7 patients with an external ventriculostomy for occlusive hydrocephalus, each of whom ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00278481
更新日期：1992-01-01 00:00:00
abstract：:For model identification and parameter estimation in the framework of linear pharmacokinetics it is most often assumed that the disposition function is a finite sum of exponential functions with time constants lambda i and associated coefficients Ci. Least-square fitting procedures are used to estimate the coefficient...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315312
更新日期：1993-01-01 00:00:00
abstract：OBJECTIVE:The aim of the present study was to investigate the pharmacokinetic profile of tramadol hydrochloride in neonates, born from mothers who underwent analgesia with tramadol for the relief of labour pain. METHODS:Intramuscular tramadol (100--250 mg) was administered to 22 mothers giving birth who requested pain...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0955-0
更新日期：2005-08-01 00:00:00
abstract：OBJECTIVE:Theophylline is metabolized to 1,3-dimethyluric acid (1,3-DMU), 3-methylxanthine, and 1-methylxanthine by CYP1A2 and partly by CYP2E1. Because 1,3-DMU is the major metabolite of theophylline, the 1,3-DMU/theophylline ratio is viewed as a good indicator of theophylline metabolic clearance. Here, we investigate...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-006-0165-4
更新日期：2006-08-01 00:00:00
abstract：:The new competitive histamine H2-receptor antagonist, ramixotidine 2 HCl (CM 57755), has been tested in healthy male volunteers for its ability to inhibit pentagastrin-stimulated gastric acid secretion. In the first study, in 8 subjects, pentagastrin 6 micrograms.kg-1 was injected s.c., 90 min after the following 4 or...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00637671
更新日期：1987-01-01 00:00:00
abstract：PURPOSE:The present study was carried out in order to assess the effects of chronic administration of flunitrazepam (as an oral hypnotic) on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. MATERIALS AND METHODS:Following a 2-week placebo run-in period, 28 healthy volunteers (13 males and 15 femal...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-018-2466-9
更新日期：2018-08-01 00:00:00
abstract：:Bay m 1099 is a newly developed inhibitor of intestinal alpha-glucosidase. Its ability to lower postprandial plasma glucose, serum insulin and C-peptide levels in Type II diabetics has been investigated. Fifteen obese Type II diabetic patients with inadequate metabolic control during sulphonylurea treatment received a...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00607953
更新日期：1986-01-01 00:00:00
abstract：OBJECTIVE:The present study was undertaken to investigate the possible effects of various agents on thiopurine methyltransferase (TPMT) activity in red blood cells (RBCs) from patients with chronic inflammatory bowel disease (IBD). METHODS:In three groups of patients with very high, normal and intermediate TPMT activi...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0950-5
更新日期：2005-07-01 00:00:00
