Abstract:
OBJECTIVE:Troglitazone is an agonist of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which has been shown to improve the metabolic control of type 2 diabetes. Troglitazone undergoes hepatic metabolism to an inactive sulphate conjugate and an oxidative quinone metabolite with minor activity. The objective of this study was to compare the pharmacokinetics of troglitazone in patients with hepatic insufficiency and normal subjects. METHODS:Three groups of eight subjects with normal liver function and moderate or severe hepatic impairment (Pugh-Child classification) completed this open study. Subjects received a single 400-mg dose of troglitazone 30 min after breakfast. Plasma concentrations of troglitazone and its metabolites were measured and standard pharmacokinetic parameters derived. RESULTS:A 46% increase in area under the plasma concentration-time curve (AUClast) was observed for troglitazone, together with a 154% increase for the quinone metabolite in the patients with moderate hepatic impairment compared with normal subjects, but these did not reach statistical significance. Corresponding increases of 18% and 53% in the severe group also failed to reach statistical significance. For the sulphate conjugate, the AUClast values for both moderate and severe hepatic impairment were in the order of fourfold higher than those in the normal group. There were reductions in the maximum observed plasma concentration (Cmax) of troglitazone to 61% of the normal group in the severe group for troglitazone, and twofold increases in sulphate metabolite Cmax in the moderate and severe groups. There was an approximately threefold increase in the half-life of the sulphate conjugate in subjects with both moderate and severe impairment of liver function compared with normal individuals. First times to maximum concentrations of troglitazone, its sulphate conjugate and the quinone metabolite were significantly longer in all severely impaired subjects compared with those with normal hepatic function, although the range was wide in all cases. Plasma protein binding was high in all subjects measured (mean unbound fraction range 0.7-5.1%), but there were insufficient samples to compare across groups. CONCLUSION:The formation of metabolites of troglitazone following a single dose is not impaired in the presence of reduced liver function although the capacity to eliminate the metabolites is altered. The clinical significance of the effect of liver disease on the conjugates is not clear.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Ott P,Ranek L,Young MAdoi
10.1007/s002280050514subject
Has Abstractpub_date
1998-09-01 00:00:00pages
567-71issue
7eissn
0031-6970issn
1432-1041journal_volume
54pub_type
临床试验,杂志文章abstract::Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00279976
更新日期:1991-01-01 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:OBJECTIVE:The aim of our study was to investigate the effects of carbamazepine (CBZ) and oxcarbazepine (OXCBZ) on aminothiol levels, including homocysteine (Hcy), cysteine, and cysteinylglycine, in chronically treated patients. METHODS:Epileptic patients receiving CBZ or OXCBZ were recruited as part of routine clinica...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-007-0388-z
更新日期:2008-01-01 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::An aqueous solution of 35S-ampicillin and polyethylene glycol (PEG 4000, unabsorbable marker) was administered orally to 6 healthy subjects with gastrointestinal tubes. The minimal absorption of radioactive material, as shown by urinary excretion of label, differed markedly between subjects and averaged 44% (25-67). A...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00614007
更新日期:1975-12-19 00:00:00
abstract:OBJECTIVE:This study was performed to investigate whether it is possible to use saliva instead of blood usually used for therapeutic drug monitoring (TDM) of disopyramide. METHODS:Six healthy male volunteers ingested 200 mg of disopyramide base, and the disopyramide concentrations in saliva and plasma (total and unbou...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050250
更新日期:1997-01-01 00:00:00
abstract::The binding of ibuprofen to human serum albumin, normal plasma and plasma obtained from rheumatoid arthritic patients was studied using the method of ultracentrifugation. It was found that ibuprofen is more strongly bound to normal plasma than to human serum albumin although this result is probably explained by fatty ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542526
更新日期:1983-01-01 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:OBJECTIVE:Databases of subjects receiving antidepressants provide evidence on the use of drugs in typical patients and settings under real-world conditions. This study analysed a general practice database to estimate the prevalence of antidepressant drug use, describe the use of these compounds by gender and age and es...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280100361
更新日期:2001-10-01 00:00:00
abstract:OBJECTIVE:Iloprost is a potent PGI2 mimetic, which has been shown to be therapeutically effective in several vascular disorders. Due to its rapid clearance from the central compartment, iloprost is administered mainly by i.v. infusion, which limits its use to hospitalized patients. In order to improve pharmacotherapeut...
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/s002280050336
更新日期:1997-01-01 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::The diabetogenic effect of deflazacort (DF), an oxazolinic synthetic corticosteroid, was studied in 12 healthy adult subjects with a positive family history of diabetes mellitus. Three oral glucose tests (oGTT) were performed at 9.00 a.m., after a 12 h fast, following randomized administration of Placebo (PL), or Defl...
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/BF00542555
更新日期:1982-01-01 00:00:00
abstract:OBJECTIVE:The goal of this study was to determine the frequencies of important allelic variants of two drug targets, dipeptidyl carboxypeptidase ( DCP1) and cholesteryl ester transfer protein ( CETP), and two other drug receptors, beta-2 adrenergic receptor ( ADRB2) and 5-hydroxy tryptamine 2A receptor ( HTR2A), in the...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-002-0423-z
更新日期:2002-04-01 00:00:00
abstract:PURPOSE:To conduct a mechanistic investigation of the interaction between aliskiren and grapefruit juice in healthy subjects. METHODS:Twenty-eight subjects received an oral dose of aliskiren 300 mg (highest recommended clinical dose) with 300 mL of either water or grapefruit juice in a two-way crossover design. Safety...
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/s00228-011-1167-4
更新日期:2012-05-01 00:00:00
abstract::The effect beta-adrenoceptor blockade on the pressor response to tyramine has been investigated in 6 healthy volunteers, each submitted to an i.v. tyramine pressor test before and after 7 days of propranolol 40 mg b.d. or indenolol 60 mg o.d. Tyramine was given as i.v. boluses of 1-6 mg, alternating with saline, in a ...
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/BF00540953
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:To determine whether two of the major operational stressors associated with military missions in Afghanistan: dry heat and long durations of soldier patrol (SP), alter the pharmacokinetics of ibuprofen. METHODS:Thirteen healthy and physically fit participants (19-32 years) were randomized to a four-arm crossov...
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/s00228-012-1307-5
更新日期:2013-01-01 00:00:00
abstract::The pharmacokinetics of phenytoin was studied in 66 epileptic Chinese children and adults. The data were analysed by the population approach, using the non-linear mixed effect model, in the MULTI (ELS) program. There was no age or gender-related effect on either the apparent maximum elimination rate (kmax) or Michaeli...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00280055
更新日期:1990-01-01 00:00:00
abstract::A comparative pharmacokinetic study was performed with two types of suppository each containing 20 mg piroxicam. The bioavailability of piroxicam was studied in 24 healthy volunteers in a double blind, randomised, cross over study. No significant difference was found in the pharmacokinetic parameters [AUC(0-72 h), AUC...
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/BF02333031
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:The aim of our study was to evaluate the impact of CYP3A4, CYP3A5, and ABCB1 polymorphisms on donepezil disposition and clinical outcome. METHODS:Fifty-four Italian patients diagnosed with probable mild to moderate Alzheimer's disease, treated with donepezil (37 patients 5 mg/day, 17 patients 10 mg/day) were g...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-010-0883-5
更新日期:2011-01-01 00:00:00
abstract:OBJECTIVE:Valsartan (V), a specific inhibitor of the angiotensin II receptor subtype, AT1, has been developed for treatment of hypertension. Combination therapy with a beta-adrenoceptor blocking agent might be considered in cases with insufficient efficacy of V alone. Therefore, an interaction trial was performed to ev...
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/s002280050318
更新日期:1997-01-01 00:00:00
abstract::The systemic elimination of nicardipine has been studied by an initial oral administration of nicardipine followed 1.25 h later by intravenous injection of the deuterium-labelled molecule (D3 nicardipine). To check that intravenous kinetics was not modified by the oral administration, an i.v. injection of unlabelled n...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00558504
更新日期:1989-01-01 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:OBJECTIVE:To investigate the effects of rifampicin on the pharmacokinetics of itraconazole in humans. METHODS:Our study was conducted with six healthy normal volunteers and three AIDS patients. All subjects received a 200 mg single dose of oral itraconazole on day 1 and day 15 and 600 mg of oral rifampicin once daily ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050437
更新日期:1998-04-01 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:PURPOSE:Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their ratios during pr...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1944-6
更新日期:2015-12-01 00:00:00
abstract::The possible interaction between cetirizine 2 HCl and alcohol was studied in a double-blind, cross-over trial in 36 healthy volunteers. The performance of each volunteer was tested with a battery of five objective psychometric tests, and their subjective feelings were evaluated by visual analogue scales, and by extens...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00615227
更新日期:1988-01-01 00:00:00
abstract::We have studied the kinetics of a single oral dose of mefloquine (750 mg) in 12 Thai patients with falciparum malaria and have compared the results with those of a previous study in 12 healthy Thai volunteers. All the patients responded to treatment with a mean parasite clearance time of 66.6 h and a mean fever cleara...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00637607
更新日期:1988-01-01 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: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:OBJECTIVE:The primary objective was to evaluate the effect of 7 days treatment with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and platelet aggregation ex vivo were investigated as a secondary objective. METHOD:A randomised, double-blind, placebo-controlled, parallel group, single centre stu...
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/s002280050479
更新日期:1998-07-01 00:00:00