Abstract:
:Since little is known of the number and types of binding sites on alpha 1-acid glycoprotein (AAG) and because drug-drug protein binding interactions often fail to fit a simple model, a study of the effect of 9 known AAG binding drugs on lidocaine free fraction (LFF) was performed. Serum was obtained from 10 healthy males, pooled and various concentrations (from 0.15 to 1000 micrograms/ml) of amitriptyline, bupivacaine, chlorpromazine, disopyramide, imipramine, meperidine, nortriptyline, propranolol and quinidine were added. LFF was determined by equilibrium dialysis at an initial lidocaine concentration of 2.0 micrograms/ml. LFF increased from 0.30 +/- 0.019 (mean +/- SD) in the absence of displacing agents to maximum values ranging from 0.59 (nortriptyline) to 0.73 (bupivacaine). Plots of LFF vs. the logarithm of displacing drug concentration yielded simple sigmoidal curves in all cases. LFF was increased 50% by an initial bupivacaine concentration of 6.0 micrograms/ml with all other drugs requiring more than 10 micrograms/ml to increase LFF to that extent. Lidocaine binding in a 4.5 g/dl albumin solution was unaffected by concentrations of quinidine, meperidine, nortriptyline and bupivacaine up to 200 micrograms/ml. Addition of AAG to serum reduced LFF as expected. A plot of the reciprocal of bound drug concentration vs. the reciprocal of free drug concentration in the presence and absence of quinidine suggested a competitive binding interaction. These data indicate that the binding interactions between lidocaine and the various displacing compounds are not significantly complicated by cooperative effects and that, with the possible exception of bupivacaine, displacement of lidocaine by any of these drugs is likely to be of clinical significance.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Goolkasian DL,Slaughter RL,Edwards DJ,Lalka Ddoi
10.1007/BF01037957subject
Has Abstractpub_date
1983-01-01 00:00:00pages
413-7issue
3eissn
0031-6970issn
1432-1041journal_volume
25pub_type
杂志文章abstract:OBJECTIVE:Losartan was given to subjects with known phenotypes of the polymorphic enzymes CYP2D6 and CYP2C19 to study any possible influence on the metabolism of the drug. METHODS:Plasma concentrations of losartan and E-3174 were studied after oral intake of 50 mg losartan in 24 healthy, male, Swedish Caucasian subjec...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050629
更新日期:1999-06-01 00:00:00
abstract::The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mean plasma half-life ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558162
更新日期:1989-01-01 00:00:00
abstract::The role of acetylator phenotype in determining the response to hydralazine when it was added to diuretic and beta-blocker at doses not exceeding 200 mg daily was examined in 57 hypertensive patients. 81% of rapid acetylators needed 200 mg hydralazine daily compared to 38% of slow acetylators (p less than 0.01). Despi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00546706
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:To investigate the distribution of plasma apixaban levels and their relationships with clinical outcomes in elderly patients with atrial fibrillation (AF). METHOD:The J-ELD AF Registry is a multicenter prospective observational study of Japanese non-valvular AF patients aged ≥75 years taking an on-label dose o...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-02896-y
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:The aim of the study was to determine the changes in consumption of psychotropic drugs by children aged less than 18 years during the years 1995 to 2001 in the Netherlands. METHODS:The year prevalence of antipsychotics, benzodiazepines, antidepressants and psychostimulants for boys and girls under 18 years w...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-004-0765-9
更新日期:2004-07-01 00:00:00
abstract:OBJECTIVE:Gentamicin population pharmacokinetics in newborns were studied with special reference to possible gender effects. METHODS:Steady-state serum levels ( n=139) were obtained from 79 neonates with a mean birth weight of 2.1 kg, mean gestational age of 35.1 weeks and mean age at the time of sampling of 4.2 days....
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-003-0663-6
更新日期:2003-12-01 00:00:00
abstract:PURPOSE:To explore and compare the opinions of physicians, pharmacists and potential users on the readability of a package insert of an over-the-counter medicine. METHODS:Exploratory study based on the administration of a semi-open questionnaire. This instrument was developed according to the readability guideline of ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-014-1645-6
更新日期:2014-05-01 00:00:00
abstract::6beta-Hydroxycortisol (6beta-OHF) urinary excretion has, for a long time, been considered a marker of drug induction and, more recently, of drug inhibition in humans and in laboratory animals, but its specificity is still under debate. In this work, we review 277 papers devoted to 6beta-OHF urinary excretion. We have ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-003-0690-3
更新日期:2003-12-01 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:OBJECTIVE:To investigate the potential for pharmacokinetic interactions between moexipril, a new converting enzyme inhibitor, and hydrochlorothiazide after single dose administration. METHODS:12 healthy male volunteers were studied by an open, randomised, three-way cross-over design, in which single doses of moexipril...
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/s002280050209
更新日期:1996-01-01 00:00:00
abstract:OBJECTIVE:High-density lipoprotein (HDL)-associated antioxidant paraoxonase (PON) may reduce low-density lipoprotein (LDL) oxidation and prevent atherosclerosis. The aim of this present study was to investigate the effect of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin on hydroge...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-004-0820-6
更新日期:2004-12-01 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 purpose of this study was to examine the influence of cigarette smoking and gender on the pharmacokinetics of metoprolol. Eighteen volunteers with no evidence of clinical disease each randomly received the following doses of metoprolol tartrate: 100 mg orally, 200 mg orally and 20 mg as a constant-rate intravenous...
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/BF00637630
更新日期:1987-01-01 00:00:00
abstract::Ple 1053 (Azosemid) is a diuretic which resembles furosemide chemically and in its mode of action. When administered intravenously, Ple 1053 was approximately 5 times more potent on a weight basis than furosemide, its dose-response relationship was closer and the slope was steeper. After oral administration Ple 1053 a...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF02089953
更新日期:1978-11-27 00:00:00
abstract::The duration of action of tiapamil was assessed in ten patients with stable exertional angina. Maximal symptom-limited treadmill exercise electrocardiography was performed before and at 1, 3, 6 and 9 h after therapy. Significant differences were only found at 1 h after tiapamil with increases in mean exercise duration...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00543965
更新日期:1987-01-01 00:00:00
abstract:OBJECTIVES:To compare 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrates for the methylation reaction catalysed by the enzyme thiopurine S-methyltransferase (TPMT). METHODS:TPMT activity in haemolysed red blood cells of healthy blood donors was determined twice, using the same experimental setting and equa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000137
更新日期:2000-07-01 00:00:00
abstract:OBJECTIVE:In patients with schizophrenia, risperidone and olanzapine are the two most commonly used atypical anti-psychotics. A recent meta-analysis based on randomized trials suggests that, in the long term, olanzapine can have a lower frequency of treatment discontinuation (or dropout) in comparison with risperidone....
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0705-0
更新日期:2004-02-01 00:00:00
abstract::A questionnaire survey was carried out to explore differences in the approach to treatment of patients with Type II diabetes between physicians in Northern Ireland, Norway and Sweden, and to discover to what extent it could account for the three-fold difference in drug use between the countries. A representative sampl...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542408
更新日期:1986-01-01 00:00:00
abstract::Some physicians regard patients of Geriatric Units as a homogeneous population with respect to digoxin dosage requirements. Others advocate the use of pharmacokinetic models in prescribing digoxin for the elderly. Sixty in-patients of Geriatric Units were studied and the results compared with those previously obtained...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF02455997
更新日期:1987-01-01 00:00:00
abstract::The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharm...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00605631
更新日期:1979-11-01 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: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::Ten healthy subjects took single oral doses of placebo, 8.8 +/- 1.8 mg motapizone, 40 +/- 13 mg captopril, 25 mg dihydralazine, 20 mg nifedipine and 4.5 +/- 1.1 mg prazosin in random order, and, as the last preparation 500 mg acetylsalicylic acid. Thrombocyte aggregation induced "ex-vivo" with collagen, ADP and adrena...
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/BF00613515
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:To assess the influence of the P450 oxidoreductase 28 SNP (POR 28) on tacrolimus pharmacokinetics in the Chinese population. METHODS:Seventy-one healthy Chinese volunteers enrolled in the study received an oral dose of 2 mg of tacrolimus after providing written informed consent. CYP3A5 3 was genotyped by polym...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-012-1432-1
更新日期:2013-04-01 00:00:00
abstract:OBJECTIVE:As quinine is mainly metabolised by human liver CYP3A4 and grapefruit juice inhibits CYP3A4, the effect of grapefruit juice on the pharmacokinetics of quinine following a single oral dose of 600 mg quinine sulphate was investigated. METHODS:The study was carried out in ten healthy volunteers using a randomis...
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/s002280050646
更新日期:1999-07-01 00:00:00
abstract:PURPOSE:Serotonin receptor 1B (HTR1B) is involved in the regulation of the serotonin system, playing different roles in specific areas of the brain. We review the characteristics of the gene coding for HTR1B, its product and the functional role of HTR1B in the neural networks involved in motivation and memory; the cent...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-009-0724-6
更新日期:2010-01-01 00:00:00
abstract::The concentrations of thiamin and thiamin monophosphate and diphosphate in plasma and whole blood samples were assessed in six healthy subjects for 12 h and in urine for 24 h following an IV and PO bolus dose of 50 mg thiamin HCl. Unphosphorylated thiamin increased rapidly in plasma after IV administration and then de...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315284
更新日期:1993-01-01 00:00:00
abstract:OBJECTIVE:UDP-glucuronosyltransferases (UGTs) UGT1A9 and UGT2B7 are involved in the metabolism of antimalarial dihydroartemisinin and antiretroviral zidovudine. Our aim was to analyze the prevalence of UGT1A9 (chromosome 2) and UGT2B7 (chromosome 4) nonsynonymous single nucleotide polymorphisms (SNPs) in West African (...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-006-0206-z
更新日期:2007-01-01 00:00:00
abstract:PURPOSE:People with dementia may have indications for aspirin prescription and clinicians are asked to balance the potential risks against benefits. This review examines the evidence for the risk and benefit of long-term aspirin use in people with dementia aged over 65 years, including randomised controlled trials and ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-021-03089-x
更新日期:2021-01-22 00:00:00
abstract::The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20-40% of that after pregnancy. The plasma half-lives of metoprolol were about th...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00613820
更新日期:1983-01-01 00:00:00