Abstract：
:Amitriptyline has clinically important interactions with ethanol. Five healthy volunteers received 25 mg of amitriptyline orally, preceded by one hour and followed for eight hours by oral ethanol (or juice), dosed to achieve and maintain blood ethanol concentrations of 800 mg/l. In the presence of ethanol, amitriptyline free plasma concentrations were increased by a logarithmic mean of 204%, 186% and 127% at 1.5, 2, and 2.5 h, respectively, and amitriptyline free AUC0-8h was increased by 48% +/- 13% (means +/- SEM) (t = 5.21, p less than 0.01). Nortriptyline total AUC0-8h was increased by 26.6% +/- 12% (means +/- SEM) (t = 2.21, p less than 0.09). At the time of peak amitriptyline plasma concentrations, mean postural sway was increased over baseline by 92% with, and 2% without ethanol; likewise, mean short term memory (word recall) was decreased over baseline by 71% with, and 37% without ethanol. Ethanol increases free amitriptyline plasma concentrations most dramatically during the period of drug absorption; this is due to a decrease in amitriptyline hepatic clearance, resulting in decreased first-pass extraction. Together with the pharmacodynamic interaction, the kinetic changes provide a rationale for the toxicity of this combination and its deleterious effects on psychomotor skills.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Dorian P,Sellers EM,Reed KL,Warsh JJ,Hamilton C,Kaplan HL,Fan Tdoi
10.1007/BF01037943subject
Has Abstractpub_date
1983-01-01 00:00:00pages
325-31issue
3eissn
0031-6970issn
1432-1041journal_volume
25pub_type
杂志文章abstract：OBJECTIVE:In vitro studies with human liver microsomes have suggested that the oxidative conversion of mexiletine (MX) to its metabolites is catalyzed by CYP2D6 and is significantly impaired in microsomes with the CYP2D6*10/*10 genotype. Therefore, we examined the influence of the CYP2D6*10 allele on MX pharmacokinetic...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-003-0656-5
更新日期：2003-09-01 00:00:00
abstract：PURPOSE:LCZ696 (sacubitril/valsartan), an angiotensin receptor neprilysin inhibitor, is indicated for chronic heart failure (HF) and reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and hospitalization for HF. Following oral administration, LCZ696 provides systemic exposure to valsartan and ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2072-7
更新日期：2016-09-01 00:00:00
abstract：PURPOSE:The quality of drug therapy is an important issue for nursing homes. This study aimed to assess the prevalence of polypharmacy and potentially inappropriate medications (PIMs) in a large sample of nursing home residents by using the data recorded during the preparation of pill dispensers. METHODS:This is a cro...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2193-z
更新日期：2017-05-01 00:00:00
abstract：BACKGROUND:Maintenance of the structural and functional integrity of the skeleton is a critical function of a continuous remodeling driven by highly associated processes of bone resorption and synthetic activities driven by osteoclasts and osteoblasts, respectively. Acceleration of bone turnover, accompanied with a dis...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-006-0174-3
更新日期：2006-10-01 00:00:00
abstract：OBJECTIVE:Entacapone is a peripherally acting catechol O-methyltransferase (COMT) inhibitor used as an adjunct to each daily levodopa/dopa decarboxylase (DDC) inhibitor dose in the treatment of Parkinson's disease. Parkinsonian patients with advanced disease and motor fluctuations take several doses of levodopa daily, ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050657
更新日期：1999-08-01 00:00:00
abstract：:Oral and sublingual isoxsuprine 20 mg were compared with placebo in double blind randomised cross over trial in 7 patients with Raynaud's phenomenon. Skin thermography, plethysmography of the finger tips and direct temperature measurements showed that sublingual isoxsuprine was slightly but consistently superior to th...
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/BF00615400
更新日期：1981-01-01 00:00:00
abstract：:The pharmacokinetics of ethanol in plasma and whole blood have been investigated and the results used to estimate the volume of total body water (TBW) by means of the dilution principle. Fifteen men (mean age 62 y) were given 0.6 g ethanol/kg body weight as an intravenous infusion over 1 h. The peak concentration of e...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00280133
更新日期：1992-01-01 00:00:00
abstract：:The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and diuretic. After a 50 mg oral dose mean (+/- SD) peak plasma concentration of T was 1.13 +/- 0.29 micrograms/ml-1 and occurred 0.79 +/- 0.40 h...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00568397
更新日期：1981-01-01 00:00:00
abstract：:The cardiovascular and respiratory actions of the adrenergic beta adrenoceptive drug sotalol have been studied in an open, short term trial. Fifteen patients with angina performed standardized orthostatic and exercise tests before and after injection of 20 mg sotalol intravenously. Although there was a significant red...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00562313
更新日期：1975-08-14 00:00:00
abstract：OBJECTIVE:To study the influence of CYP3A4 inhibition by ketoconazole on the disposition of venlafaxine in individuals with different CYP2D6 pheno- and genotypes. METHODS:In an open two-phase study, 21 healthy volunteers with known CYP2D6 pheno- and genotype [14 extensive metabolisers (EMs), 7 poor metabolisers (PMs)]...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-003-0627-x
更新日期：2003-09-01 00:00:00
abstract：:Jejunal perfusion was performed in 12 healthy volunteers to evaluate the dose dependent effects of loperamide on intestinal absorption, stimulated secretion and transit. In 6 volunteers intestinal perfusion of the jejunal segment with isotonic NaCl solution was followed by addition of loperamide in increasing doses (2...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315436
更新日期：1991-01-01 00:00:00
abstract：:To elucidate the effect of Nicorandil on myocardial energy metabolism and myocardial sympathetic activity, we administered Nicorandil orally to eight patients with angina pectoris prior to exercise testing. Arterial and coronary sinus levels of lactate, ammonia, hypoxanthine (HX), adrenaline and noradrenaline were mea...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00198297
更新日期：1995-01-01 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：:Red cell folate concentrations were determined in 74 epileptic women in early pregnancy in a prospective study. All patients were treated continuously with antiepileptic drugs since before conception. The most frequently used drugs were carbamazepine (n = 39) and phenytoin (n = 26). Sixty-four patients (86%) were on m...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00198317
更新日期：1995-01-01 00:00:00
abstract：BACKGROUND:Fexofenadine is the active metabolite of the non-sedating anti-histamine terfenadine. Pre-licensing clinical trials in over 6000 patients suggested it was effective and well tolerated. OBJECTIVE:To assess the tolerability and safety of fexofenadine immediately after its availability on the UK market in Marc...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100292
更新日期：2001-07-01 00:00:00
abstract：BACKGROUND:Visual hallucinations (VHs) are frequent non-motor complication of Parkinson's disease (PD), associated to a negative prognosis. Previous studies showed an association between dopamine receptor (DR) gene (DR) variants and psychosis in Alzheimer's disease, addictions, schizophrenia, and bipolar disorder. Howe...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2111-4
更新日期：2016-11-01 00:00:00
abstract：PURPOSE:Bosutinib is an oral, dual Src and Abl tyrosine kinase inhibitor (TKI) approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia resistant or intolerant to prior TKI therapy. Bosutinib is primarily metabolized by cytochrome P450 (CYP) 3A4, suggesting drug interaction potential with...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-016-2108-z
更新日期：2017-01-01 00:00:00
abstract：:Investigations were undertaken to evaluate which uraemic solutes decrease drug protein binding. This was done by performing HPLC-fractionation of uraemic biological fluids and studying the effect of addition of a lyophilisate of each fraction to normal plasma containing standard quantities of radiolabelled drugs. From...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/BF01428386
更新日期：1993-01-01 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：:Changes in venous haemodynamics were studied after administration of a single dose of 3 g Heptaminol Adenosine Phosphate (HAP) to 30 subjects with primary varicose veins. Strain gauge plethysmography was used to observe changes in venous volume and in maximal venous outflow, 1, 2, 3 and 4 h after dosing. A significant...
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/BF00609421
更新日期：1989-01-01 00:00:00
abstract：PURPOSE:The objective of this work was to develop a population pharmacokinetic model for a prolonged-release granule formulation of valproic acid (VPA) in children with epilepsy and to determine the doses providing a VPA trough concentration (Ctrough) within the target range (50-100 mg/L). METHODS:Ninety-eight childre...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-018-2444-2
更新日期：2018-06-01 00:00:00
abstract：:In Belgium, all dispensed drugs are provided with package inserts. Traditional physician-orientated inserts are gradually being replaced by patient package inserts (PPIs). The present survey is focused on the use of inserts for antihypertensive drugs and their impact on the reported occurrence and attribution of adver...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00316093
更新日期：1990-01-01 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：:The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00614557
更新日期：1988-01-01 00:00:00
abstract：:A double blind, placebo-controlled study of the ventilatory effects of three new beta 1-selective adrenoceptor blockers was carried out in eight asthmatic patients. Measurements were performed before and 2, 3 and 4 h after ingestion of a single oral dose of placebo, atenolol 100 mg, metoprolol 100 mg or acebutolol 400...
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/BF00542093
更新日期：1981-01-01 00:00:00
abstract：:The acute effect of a single oral dose of isradipine 5 mg on blood pressure, renal haemodynamics, electrolyte excretion and plasma renin activity was studied in 10 healthy males. Isradipine did not produce a significant change in systolic or diastolic blood pressure, and glomerular filtration rate, renal plasma flow, ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00315405
更新日期：1990-01-01 00:00:00
abstract：OBJECTIVE:To assess the potential damage to patients from the inappropriate use of placebo. METHODS:Pivotal clinical trials of new drugs were evaluated for the treatment of multiple sclerosis following effective treatment with beta interferons and glatiramer acetate. The differences in the relapse rate between the exp...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1383-6
更新日期：2013-03-01 00:00:00
abstract：:The pharmacokinetic profiles of transdermal timolol 6 and 24 mg (as 5 and 20% w/v patches) was studied in four healthy young volunteers. To assess its bioavailability, the pharmacokinetics of an IV infusion of timolol maleate 5 mg was also determined in the same subjects. When the 20% (w/v) timolol patch was applied, ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315551
更新日期：1993-01-01 00:00:00
abstract：:To evaluate the influence of the stomach and the cholinergic system on gallbladder contraction induced by physiological stimuli, the reduction in gallbladder volume in 7 healthy volunteers has been studied by real-time ultrasonography after the oral and intraduodenal administration of olive oil, preceded by pretreatme...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00315412
更新日期：1990-01-01 00:00:00
abstract：OBJECTIVE:Use of analgesic drugs in acute renal colic varies widely in different countries. In order to assess the prescribing patterns in acute renal colic in French emergency departments (EDs), the present study compared intentions of prescription, real prescription and evidence-based data in a sample of emergency pr...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100366
更新日期：2001-11-01 00:00:00
