Abstract:
:Differences in the plasma concentrations of drugs after oral administration are caused by two main factors: variation in absorption ratios and in the distribution processes in the body. A new method for the dissection of both types of factors is discussed. The method uses a reference regression of the AUC-values to the corresponding values after intravenous infusion of graded doses. The reference regression is estimated from an appropriate trial. Deviation of the determined AUC-values from the regression curve afford an estimate of the residual variance due to varying distribution volumes or similar random biological effects. For the estimation of absorption ratios after oral administration the drug is given orally to another sample of subjects and their AUC-values are calculated. The deviation of these AUC values due to the above mentioned random effects are simulated using the residual variance of the reference regression, and are subtracted from the observed AUC-values. Then, the differences in the corresponding absorbed doses are transformed by inverting the reference regression. From these doses the empirical distribution function and statistical parameters (e.g. quantiles) are determined. The method has the advantage that no restrictive assumptions are required, such as first order processes, dose linearity, homogeneity of variance or normal distribution of absorption ratios. Its applicability to substances with qualitative differences in their pharmacokinetics is demonstrated by appropriate examples.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Betzien G,Kaufmann B,Schneider Bdoi
10.1007/BF00545226subject
Has Abstractpub_date
1982-01-01 00:00:00pages
265-72issue
3eissn
0031-6970issn
1432-1041journal_volume
22pub_type
杂志文章abstract:OBJECTIVE:Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the pharmacokinetic interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-016-2048-7
更新日期:2016-06-01 00:00:00
abstract:OBJECTIVES:To assess (1) whether the utilisation of codeine or propoxyphene differs among the three major Swedish cities (Stockholm, Göteborg and Malmö) and between urban and semirural areas; (2) if so, whether it co-varies with the utilisation of other potentially dependence-promoting drugs, benzodiazepines; (3) what ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050680
更新日期:1999-10-01 00:00:00
abstract:OBJECTIVE:To study the effect of renal impairment on the pharmacokinetics of sertindole. METHODS:A single 4 mg oral dose of sertindole was given to normal subjects (n = 6) and subjects with various degrees of impaired renal function (n = 18) classified into mild, moderate, and severe/hemodialysis based on their creati...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050278
更新日期:1997-01-01 00:00:00
abstract::The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00266354
更新日期:1992-01-01 00:00:00
abstract::Prazosin is a post synaptic alpha adrenergic blocker effective in hypertension, whose hypotensive effect is unaccompanied by reflex tachycardia or hyperreninemia, nor by other evidence of increased sympathetic activity. We studied the baroreceptor reflex arc as a potential mediator of these effects. Twenty-two essenti...
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/BF00606418
更新日期:1982-01-01 00:00:00
abstract::The haemodynamic effects of intravenous metoprolol, over the dose-range 2.5--20 mg, were studied in 12 patients with coronary heart disease. The pharmacodynamic activity of the drug was confirmed by the suppression of exercise systolic pressure and tachycardia. There were statistically significant dose-response reduct...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00544581
更新日期:1981-01-01 00:00:00
abstract::Sixty patients were treated for 1 year for essential uncomplicated hypertension, 30 with beta-blockers alone (BB) and 30 with BB and chlorthalidone (CTD). BB did not affect serum K+ or Mg++. In the BB-group there was a statistically significant trend towards retention of Mg++ in a loading test, but the effect was clin...
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/BF00543964
更新日期:1987-01-01 00:00:00
abstract::The bioavailability of a new controlled release formulation of indomethacin lysine salt in tablets was tested in 6 healthy humans against a conventional indomethacin lysinate formulation in capsules. Both contained 100 mg of the drug, i.e. 70 mg indomethacin. Peak plasma levels were lower and more lasting and the AUC ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609963
更新日期:1987-01-01 00:00:00
abstract:BACKGROUND:Monoamine oxidase inhibitors (MAOIs) are uncommonly used due to their high frequency of adverse effects, including tachycardia and hypertension. Recently, there has been renewed interest in the role of this class of drugs in treating a variety of psychiatric disorders. The clinical features of MAOI overdose ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-007-0360-y
更新日期:2007-11-01 00:00:00
abstract::Seven patients with acutely elevated diastolic blood pressure (DBP greater than or equal to 135 mmHg) were treated with repeated injections of diazoxide 1 mg/kg body weight i.v. at 10-min intervals. If the DBP was not reduced to 110 mmHg or less after 5 injections, a dose of 5 mg/kg was given. Serum diazoxide (total a...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00613809
更新日期:1983-01-01 00:00:00
abstract::The effect of nomifensin (Hoechst 36984), a synthetic psychotropic drug whose structure differs from MAO inhibitors and tricyclics, was studied in a double blind comparative trial with desimipramine in patients with various depressive syndromes. Forty-three patients (23 in the nomifensin group and 20 in the desimipram...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00609468
更新日期:1976-06-15 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:PURPOSE:The purpose of this study is to investigate the effect of two of the most important functional CYP1A2 variations -3860G > A and -163C > A on carbamazepine pharmacokinetics in Serbian pediatric epileptic patients. METHODS:The study involved 40 Serbian pediatric epileptic patients on steady-state carbamazepine t...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-2006-9
更新日期:2016-04-01 00:00:00
abstract::The function of the hepatic P450 enzyme system was evaluated by measuring the kinetics of antipyrine and serum sex hormone levels were determined in 12 male patients with epilepsy during carbamazepine medication, and two and six months after changing their medication to oxcarbazepine. Antipyrine t1/2 increased and ant...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00196862
更新日期:1995-01-01 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::A new acid thiol, 2-mercaptopropionate, has been identified by GC-MS in urine from cystinuric patients on treatment with 2-mercaptopropionylglycine. The amount excreted was 50-300 mumol/24h and it was correlated with the oral dose of 2-mercaptopropionyl-glycine. The observation may be of clinical importance as the met...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00871000
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:To analyze the clinical features and risk factors of tigecycline-associated hypofibrinogenaemia and study whether cefoperazone/sulbactam combined with tigecycline aggravates coagulopathy or hypofibrinogenaemia. METHODS:A retrospective case-control study of patients with severe infection who were treated with t...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-02860-w
更新日期:2020-07-01 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: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::The influence of time of drug administration on pharmacokinetics of theophylline was studied both after ingestion of a sustained-release tablet, containing choline theophyllinate ( Zy 15061-S. R.; Teovent ; Sabidal ; ZYMA S.A.) and after intravenous infusion of aminophylline to eight healthy volunteers. Both drugs wer...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00630288
更新日期:1984-01-01 00:00:00
abstract::Right ventricular repolarisation and refractoriness after therapeutic doses of disopyramide have been studied in 10 patients with coronary artery disease by recording monophasic action potentials (MAP) during programmed stimulation. Using 2 catheters, with the tip of one in the apex and the other in the outflow tract ...
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/BF00558240
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:Drug-induced immune thrombocytopaenia is a rare, serious condition that can be triggered by numerous medications. To characterize the spectrum of drugs associated with immune thrombocytopaenia (ITP) in the Berlin Case-Control Surveillance Study (FAKOS). METHODS:Adult hospitalized patients with new onset idiopa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-011-1184-3
更新日期:2012-05-01 00:00:00
abstract::An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha 1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week run-in placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled ever...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00555503
更新日期:1988-01-01 00:00:00
abstract::The debrisoquine hydroxylation phenotype was studied in 152 unselected healthy Tasmanian subjects, who were mostly Caucasians of British ancestry. Following a 10 mg oral dose of debrisoquine (D), the ratio of D/4-hydroxydebrisoquine excreted in 8-h urine (metabolic ratio, MR) was determined. MR values were bimodally d...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315235
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Tocilizumab, a monoclonal antibody directed against the IL-6 receptor, might block detrimental effects of IL-6 on transplantation. IL-6 plays a considerable role in cytokine storm after stem cell transplantation as well as graft versus host disease, and it has also been shown to be involved in solid organ allog...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-020-02864-6
更新日期:2020-06-01 00:00:00
abstract:OBJECTIVE:To describe the quantitative and qualitative changes in the utilization of oral antihyperglycemic drugs (OAHDs) between 1998 and 2004 and to analyze patients' adherence to OAHD therapy. METHODS:We conducted a retrospective analysis of the electronic database of the Hungarian National Health Fund Administrati...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0031-9
更新日期:2005-12-01 00:00:00
abstract:PURPOSE:Adverse drug reactions as well as vitamin D deficiency are issues of public health concern in older people. However, relatively little is known about the impact of drug use on vitamin D status. Our primary aim is to explore associations between drug use and vitamin D status in older people. Furthermore, prevale...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-016-2016-2
更新日期:2016-05-01 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:PURPOSE:Anaphylaxis is a potentially fatal systemic adverse drug reaction (ADR). It is an unpredictable and mostly dose-independent event that occurs suddenly following exposure to the causative drug. Our objective was to characterize a case series of anaphylactic reactions reported to the Portuguese Pharmacovigilance ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-012-1376-5
更新日期:2013-03-01 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