Abstract：
:To study the effects of enzyme induction on its pharmacokinetics, a single oral dose of the new antiarrhythmic agent mexiletine hydrochloride 400 mg was administered to 8 healthy volunteers before and after treatment with rifampicin 300 mg b.i.d. for ten days. The absorption and distribution of mexiletine were not changed after rifampicin, but its elimination half-life fell from 8.5 +/- 0.8 h (mean +/- SE) to 5.0 +/- 0.4 h (p less than 0.01), and its nonrenal clearance increased from 435 +/- 68 ml/min to 711 +/- 101 ml/min (p less than 0.01). The mean renal clearance of mexiletine did not change, but it showed an exponential correlation with urinary pH. The amount of unchanged mexiletine excreted in urine over two days decreased from 32 +/- 7 to 18 +/- 3 mg (p less than 0.01). The half-life of antipyrine fell from 11.8 +/- 0.4 to 5.5 +/- 0.3 h and its clearance increased from 40 +/- 3 ml to 74 +/- 3 ml/min (p less than 0.01). There was a significant (p less than 0.05) positive linear correlation between both the half-lives and the clearances of antipyrine and mexiletine. The clearances were positively correlated with serum gamma-glutamyl transpeptidase. The results suggest that the dosage of mexiletine should be adjusted when enzyme inducing drugs are started or stopped during therapy with it.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Pentikäinen PJ,Koivula IH,Hiltunen HAdoi
10.1007/BF00547565subject
Has Abstractpub_date
1982-01-01 00:00:00pages
261-6issue
3eissn
0031-6970issn
1432-1041journal_volume
23pub_type
杂志文章abstract：PURPOSES:Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK o...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-013-1501-0
更新日期：2013-08-01 00:00:00
abstract：OBJECTIVE:Interindividual variability is common at all stages of drug absorption, distribution, pharmacodynamics, metabolism and elimination. In this study, we focused on two enzymes involved in phase-I drug metabolism as markers of pharmacological variability: the CYP3A and CYP2D6 subsystems of cytochrome P450. The ma...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0906-9
更新日期：2005-05-01 00:00:00
abstract：OBJECTIVE:This work aimed at building a population pharmacokinetic (PK) model for lamivudine (LMV), stavudine (STV) and zidovudine (ZDV), estimating their inter and intraindividual PK variability and investigating the influence of different covariates. METHODS:Population PK of LMV, STV and ZDV was separately evaluated...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1007/s00228-007-0337-x
更新日期：2007-11-01 00:00:00
abstract：:The effects of acute introduction and withdrawal of trimeprazine (Vallergan), an antihistaminic phenothiazine derivative with known sedative effects, were investigated by a single blind polygraphic study in 8 healthy volunteers. A baseline placebo was given on Nights 1-3, followed either by 10 mg or 20 mg of the drug ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00606405
更新日期：1977-03-11 00:00:00
abstract：PURPOSE:We previously reported that chronic heart failure (CHF) treatments reduce the duration of hospitalisation, even in elderly patients. The present study aimed to determine whether CHF treatment also provides long-term benefits in terms of reduced mortality at 8 years. METHODS:A cohort of 281 patients who were ad...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1400-9
更新日期：2013-04-01 00:00:00
abstract：OBJECTIVE:To study the main comedications associated with major bleeding during anticoagulant therapy with coumarins in a non-selected population under everyday circumstances. METHODS:The study population for this retrospective cohort study included all new users of phenprocoumon or acenocoumarol aged 40-80 years, dur...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0947-0
更新日期：2005-07-01 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：PURPOSE:The study aimed to test the hypothesis that hospital electronic prescribing and medicine administration system (HEPMA) implementation impacted patient discharge letter quality, nature and frequency of prescribing errors. METHOD:A quasi experimental before and after retrospective case note review was conducted ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-017-2274-7
更新日期：2017-10-01 00:00:00
abstract：PURPOSE:As an inhibitor of HMG-CoA reductase that catalyses the first step of cholesterol synthesis, pitavastatin undergoes little hepatic metabolism; however, it is a substrate of uptake and efflux transporters. Since pitavastatin is potentially co-administered with agents that affect transporter activities, the pharm...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-013-1554-0
更新日期：2013-11-01 00:00:00
abstract：:Ten normal adult tobacco smokers and 10 nonsmoking volunteers 20-31 years of age were the subjects of this study. The tobacco smokers all had a history of daily tobacco smoking. They were asked to stop smoking for 12 hours prior to testing. The Hoffmann (H) reflex and its recovery cycle were measured on different days...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00196110
更新日期：1994-01-01 00:00:00
abstract：PURPOSE:Time of drug administration may significantly influence its effect. The aim of the present study was to investigate the effect of ASA (administrated in the morning or in the evening) on the anti-hypertensive effect and diurnal blood pressure profile in the high-risk group of cardiovascular patients. METHODS:Al...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02997-8
更新日期：2021-01-01 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 effects of the ingestion of food and digoxin on the cardiovascular system alone and in combination have been observed in eight healthy subjects. A positive inotropic response was seen following food (2.5 MJ) and intravenous digoxin (0.01 mg/kg) with significant decreases in QS2Index (QS2I) pre-ejection period (PEP...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00615959
更新日期：1986-01-01 00:00:00
abstract：BACKGROUND:Serious adverse effects have been observed with some non-sedative H1-antihistamines (terfenadine and astemizole) when they were associated with drugs known to inhibit their metabolism. However, this is not a class effect, and this interaction should be considered on a case-by-case basis. The aim of this stud...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0917-6
更新日期：2005-06-01 00:00:00
abstract：:The pharmacokinetics of loprazolam have been studied in eight healthy male volunteers after single and repeated 2 mg oral doses taken at night, for eight nights. The absorption and disposition of unchanged drug (HPLC-GC assay) and receptor active benzodiazepine-type materials (radioreceptor assay) were examined after ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542354
更新日期：1983-01-01 00:00:00
abstract：:It was considered that double-blind crossover studies of therapeutic efficacy after acute injury could well be done in patients who required surgical removal of impacted wisdom teeth from both sides of the lower jaw. In the present trial 24 healthy patients received either placebo or ibuprofen (Brufen: 400 mg three ti...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00567117
更新日期：1975-04-04 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：PURPOSE:Higher drug concentrations in complex clinical scenarios in which multiple factors such as drug-drug interactions (DDIs) and comorbidities are simultaneously present are not necessarily rationalized in prospective clinical studies. Physiologically based pharmacokinetic (PBPK) modeling and simulation of the anti...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02861-9
更新日期：2020-06-01 00:00:00
abstract：PURPOSE:Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-016-2062-9
更新日期：2016-08-01 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：PURPOSE:Older people with several chronic conditions require multiple drugs from different classes to be adequately treated. This study aims to: (i) measure medication adherence across multiple conditions and therapeutic drug groups in older community-dwelling patients, and (ii) examine the effect of multimorbidity on ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1007/s00228-017-2388-y
更新日期：2018-03-01 00:00:00
abstract：:The metabolic fate and ACTH-suppressant activity of two injectable dexamethasone esters, 21-phosphate and 21-sulphate, were studied in healthy men. After i.v. injection of 20mg free steroid alcohol, dexamethasone phosphate was efficiently hydrolyzed to free dexamethasone, reaching its peak plasma concentration within ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00618778
更新日期：1981-01-01 00:00:00
abstract：:Three groups of patients with biliary tract disease treated by cholecystectomy were given ceftriaxone. In Group 1 single doses of 150 mg and 1500 mg were given on Days 1 and 5 after cholecystectomy. In Group 2 2 g was given daily for 6 days and the cholecystectomy was on Day 2. Patients in Group 3 received 2 g every 1...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00607958
更新日期：1986-01-01 00:00:00
abstract：PURPOSE:In the past few years, several fracture-related events have been reported with chronic use of selective serotonin reuptake inhibitors (SSRIs) throughout the globe. Hence, an updated systematic review and meta-analysis was necessary to ascertain the risk involved. The present work evaluated the association of SS...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02893-1
更新日期：2020-10-01 00:00:00
abstract：OBJECTIVE:To compare the efficacy of activated charcoal and gastric lavage in preventing the absorption of moclobemide, temazepam, and verapamil 30 min after drug ingestion. METHODS:In this randomized cross-over study with three phases, nine healthy volunteers received a single oral dose of 150 mg moclobemide, 10 mg t...
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/s002280000139
更新日期：2000-07-01 00:00:00
abstract：:The influence of isosorbide dinitrate (ISDN) and food ingestion on superior mesenteric artery impedance was investigated in 24 healthy volunteers (age 40 +/- 2.7 years). Superior mesenteric artery circulation was assessed by duplex ultrasound. Pulsatility index (PI) was considered as a parameter of vascular resistance...
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/BF00196852
更新日期：1995-01-01 00:00:00
abstract：:We have studied the transfer of the analgesic ketorolac tromethamine into breast milk in ten women aged between 22 and 35 years. Ketorolac administration was started between 2 and 6 days after delivery. The breast milk was not fed to the infant because of maternal antibiotic use (6 patients) or because of jaundice of ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558080
更新日期：1989-01-01 00:00:00
abstract：:Our goal was to develop a pharmacokinetic-pharmacodynamic model that describes the fate of atracurium and its metabolite laudanosine as well as the time course of the neuromuscular block. The model was based on the consideration of mass balance of atracurium and was constructed by postulating an effect compartment lin...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00226335
更新日期：1996-01-01 00:00:00
abstract：:Plasma aspirin, salicylate and salicyluric acid concentrations were monitored in young, elderly and alcoholic subjects after ingestion of a single 1.2 g dose of soluble aspirin. The plasma aspirin, salicylate and unbound salicylate concentration-time profiles varied considerably between individual subjects. Most of th...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00543800
更新日期：1983-01-01 00:00:00
abstract：:The effect of acute and long-term treatment with propranolol on cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2) has been studied in 8 young healthy volunteers. CBF was measured by 133Xe-inhalation and single photon emission computer tomography, and CMRO2 was calculated from the arterio-veno...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315115
更新日期：1990-01-01 00:00:00
