Abstract：
OBJECTIVE:The effect of age on the pharmacokinetics and pharmacodynamics of prazosin (alpha 1 adrenoceptor blocker) was studied in 20 healthy volunteers. PATIENTS:Ten elderly (61-81 y) and ten young (23-28 y) subjects were studied. All subjects received 1 mg of prazosin orally in a fasting state. Serial blood samples were collected for calculation of oral pharmacokinetics, and blood pressure and pulse rate were measured during blood collection. Subjects remained supine and fasting for the first three hours post drug administration, after which they were allowed to ambulate and eat. RESULTS:The oral pharmacokinetics of prazosin were not different in the two age groups. The serum t1/2 in the elderly was 210 min while in the young group was 139 min. The AUC(zero)-infinity in the two groups was not different. The Cmax was identical in the two groups, and the time to Cmax was 84 min in the elderly and 114 min in the young subjects. Protein binding was 93.4% in the elderly and 93.5% in the young subjects and the serum alpha 1 acid glycoprotein concentration was not different in the two groups of subjects. Even though the pharmacokinetics of prazosin were unchanged by age, the haemodynamic effects of the drug were greater in the elderly. The fall in systolic blood pressure and mean blood pressure was significantly greater in the elderly group at multiple time points after drug administration while the change in diastolic blood pressure was equivalent in the two age groups. Despite a greater decrease in mean blood pressure in the elderly, the compensatory increase in heart rate was similar in the two age groups suggesting a difference in the baroreceptor reflex in the two age groups. CONCLUSION:The results of this study demonstrate that age does not alter the pharmacokinetics of oral prazosin, but the pharmacodynamic response at equivalent plasma prazosin concentration is greater in the elderly.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Andros E,Detmar-Hanna D,Suteparuk S,Gal J,Gerber JGdoi
10.1007/s002280050067subject
Has Abstractpub_date
1996-01-01 00:00:00pages
41-6issue
1-2eissn
0031-6970issn
1432-1041journal_volume
50pub_type
临床试验,杂志文章abstract：:The bronchodilator activity and side-effects of treatment for 4 days with either 0.085, 0.170 or 0.34 mg/kg bambuterol b.i.d. (a prodrug of terbutaline) or 0.071 mg/kg terbutaline t.i.d. have been evaluated over 12 h, in a double-blind, randomized crossover trial in 19 asthmatic out-patients. Plasma terbutaline concen...
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/BF00614187
更新日期：1986-01-01 00:00:00
abstract：:Carvedilol and nitrendipine were given for 12 weeks in a double-blind study to 81 elderly patients (greater than or equal to 60 years) with essential hypertension. The effects on blood pressure were measured (Riva Rocci) before medication and after 2 h with the patient in a lying and standing position after 4 weeks of...
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/BF01409490
更新日期：1990-01-01 00:00:00
abstract：:Acute studies of clonidine suggest that it lowers blood pressure by central enhancement of baroreflex sensitivity coupled with diminished evidence of sympathetic outflow, but longterm clonidine data have not been conclusive. We examined effects of one month of low dose clonidine (0.4 +/- 0.15 mg/day) alone in 13 essen...
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/BF00558378
更新日期：1981-01-01 00:00:00
abstract：OBJECTIVE:To develop quality prescribing indicators for general practitioners (GPs) who are non-monitored and not included in pay-for-performance programs, and to determine compliance with incentivized and non-incentivized indicators. STUDY DESIGN:Descriptive cross sectional study. SETTING:Aljarafe Primary Health Car...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-013-1542-4
更新日期：2013-10-01 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：:Atropine-induced bradycardia is traditionally ascribed to central vagal stimulation, although bradycardia has also been observed after administration of quarternary amines. Pirezepine, a selective M1-antagonist, causes bradycardia in therapeutic doses for which a peripheral mechanism is postulated. This hypothesis has...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558245
更新日期：1988-01-01 00:00:00
abstract：PURPOSE:To review the marketing authorization of biosimilars and provide a critical analysis of the pivotal trials supporting their approval by the European Medicines Agency (EMA). METHODS:EMA website to identify the biosimilars approved up to July 2019 and the European Public Assessment Report for information on pivo...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-019-02805-y
更新日期：2020-04-01 00:00:00
abstract：:The kinetics and dynamics of single doses (5 mg p.o.) of the optical isomers of acenocoumarol (R-AC and S-AC) were followed in healthy subjects and the effect on them of cimetidine 800 mg/day was also investigated. The AC enantiomers differed greatly in their pharmacokinetics. The mean residence time (MRT) of R-AC was...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542424
更新日期：1986-01-01 00:00:00
abstract：OBJECTIVE:To examine the effect of fluconazole, a potent inhibitor of CYP2C9 and CYP2C19, on the pharmacokinetics of rosuvastatin in healthy volunteers. Significantly increased plasma concentrations of fluvastatin have been observed following co-administration with fluconazole. METHODS:This was a randomised, double-bl...
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/s00228-002-0508-8
更新日期：2002-11-01 00:00:00
abstract：OBJECTIVE:The purpose of this study was to investigate in healthy male subjects the tolerability, pharmacokinetics, and pharmacodynamics of ascending doses of clazosentan, an intravenous endothelin receptor antagonist. METHODS:Clazosentan was infused at doses of 3-60 mg/h for 3 h, 60 mg/h for 6 h and at 30 mg/h for 12...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-006-0117-z
更新日期：2007-02-01 00:00:00
abstract：PURPOSE:The present study was carried out to investigate current prescribing and dispensing practices in the largest two teaching hospitals in Sudan and compare them with those of published studies in developing countries. METHODS:A descriptive, quantitative and cross-sectional study was conducted among hospital outpa...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0216-x
更新日期：2006-12-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to clarify the effect of genetic polymorphisms of CYP2C19 on the pharmacokinetics of phenobarbitone (PB) using a nonlinear mixed-effects model (NONMEM) analysis in Japanese adults with epilepsy. METHODS:A total of 144 serum PB concentrations were obtained from 74 subjects treated wi...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050703
更新日期：2000-02-01 00:00:00
abstract：BACKGROUND:Pharmacovigilance, defined by the World Health Organisation as 'the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem' plays a key role in ensuring that patients receive safe drugs. Our knowledge of a drug's adverse...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-008-0475-9
更新日期：2008-08-01 00:00:00
abstract：:The influence of bezafibrate treatment on hepatic cholesterol metabolism was studied in rats and in humans. The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cholesterol acyltransf...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/BF01409405
更新日期：1991-01-01 00:00:00
abstract：:The effect of nevirapine once-daily dosing on the pharmacokinetics of methadone and its main metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, was evaluated in ten HIV positive patients on stable methadone therapy. Nevirapine 200 mg once daily was administered orally from day 1 to day 14. On day 15, nevir...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-007-0299-z
更新日期：2007-07-01 00:00:00
abstract：OBJECTIVE/METHODS:The metabolism of chloramphenicol succinate (CAPS) by human bone marrow was studied in vitro using 75 marrow samples. Whole marrow samples were incubated with CAPS with or without reduced nicotinamide adenine dinucleotide phosphate for 1, 2 and 3 h at 37 degrees C. Ficoll-paque-separated marrow mononu...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280000143
更新日期：2000-08-01 00:00:00
abstract：:The pharmacodynamic effects of FCE20700, a new PGE2 derivative, have been investigated in 6 healthy volunteers given single intragastric (i.g.) and intraduodenal (i.d.) doses of 1 and 2 mg and placebo, according to a double-blind, within-subjects design. For 30-270 min following i.g. administration the effect of FCE20...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00606626
更新日期：1987-01-01 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：: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：:The effect of a single oral dose of 40 mg xipamide on urinary excretion of Na+, K+, Cl-, Ca2+ and Mg2+ in healthy subjects and in patients with varying degrees of renal impairment was compared with various conventional diuretics. Xipamide caused marked excretion of Na+ and Cl-, whereas the diuretic produced only moder...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542150
更新日期：1984-01-01 00:00:00
abstract：PURPOSE:Vancomycin (VCM) is used for the treatment of methicillin-resistant Staphylococcus aureus. Although the risk factors for VCM nephrotoxicity have been evaluated, the time course of renal function during VCM treatment is unknown. We assessed risk factors for VCM nephrotoxicity and how renal function varied over t...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-019-02648-7
更新日期：2019-06-01 00:00:00
abstract：:The mode and site of action of the new diuretic agent piretanide were investigated in man. The effect of a single oral dose of 12 mg was compared with that of furosemide 80 mg p.o. iin 6 patients with the nephrotic syndrome. Piretanide showed a greater diuretic and natriuretic response than furosemide during maximal w...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561895
更新日期：1980-01-01 00:00:00
abstract：PURPOSE:To quantify the importance of drug-drug interactions (DDIs) in the occurrence of adverse drug reactions (ADRs) reported with serotoninergic reuptake inhibitors in a pharmacovigilance database. METHODS:All spontaneous reports of ADRs registered in 2008 by the Midi-Pyrénées PharmacoVigilance Centre that containe...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-011-1156-7
更新日期：2012-05-01 00:00:00
abstract：:A new technique which combines skin microinjection of minute amounts of drugs (0.5 microliter) and measurement of capillary permeability by intravital fluorescence videomicroscopy and densitometry is introduced. Glass micropipettes with a tip diameter of 7-9 microns are inserted by a micromanipulator into the stratum ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00203779
更新日期：1996-01-01 00:00:00
abstract：BACKGROUND:Cytochrome P450 2C9 (CYP2C9) allelic variant carriers have been shown to experience hyper-responsiveness to small doses of oral anticoagulants (OAs) (warfarin or acenocoumarol) and a higher bleeding rate. OBJECTIVES:To determine the relative frequencies of different risk factors for OA overdose including di...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-002-0538-2
更新日期：2003-03-01 00:00:00
abstract：PURPOSE:Treatment failures following vancomycin therapy in patients with methicillin-resistant Staphylococcus aureus infections have led to the utilization of higher doses of this antibiotic to achieve the trough concentrations of 10-20 μg/mL recommended by the Infectious Diseases Society of America clinical practice g...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-012-1259-9
更新日期：2012-09-01 00:00:00
abstract：OBJECTIVE:In Norway, very little data are available on the relation between the total number of research projects on the clinical development of drugs that have been started, the number of these projects in which the research phase has been completed and the number of projects for which results have been published. The...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0601-8
更新日期：2009-03-01 00:00:00
abstract：OBJECTIVE:Nafamostat mesilate, a potent protease inhibitor, is widely used for the treatment of pancreatitis, disseminated intravascular coagulation and as an anticoagulant in haemodialysis. However, hyperkalaemia associated with nafamostat mesilate has been reported. It is thought to be due to decreased urinary potass...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050176
更新日期：1996-01-01 00:00:00
abstract：OBJECTIVE:The extrapolated area under the concentration-time curve (AUC0-infinity) for any drug is considered by operating guidelines as the primary parameter related to the extent of absorption in single-dose bioavailability and bioequivalence trials. Not more than 20% should be added to the experimental AUC (AUC0-t) ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050684
更新日期：1999-11-01 00:00:00
abstract：:We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Tri...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00278469
更新日期：1992-01-01 00:00:00
