Abstract:
BACKGROUND AND OBJECTIVES:Opicapone is a novel third generation catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to compare the levodopa pharmacokinetic profile throughout a day driven by the COMT inhibition either following repeated doses of opicapone or concomitant administration with entacapone. METHODS:A randomized, double-blind, gender-balanced, parallel-group study was performed in 4 groups of 20 healthy subjects each. Four subjects in each group received placebo during the entire study. Sixteen subjects in one group received placebo once daily for 11 days and on day 12, 200 mg entacapone concomitantly with each levodopa/carbidopa dose (three times separated by a 5-h interval). Sixteen subjects in each of the remaining three groups received respectively 25, 50, and 75 mg opicapone once daily for 11 days and on day 12, placebo concomitantly with each levodopa/carbidopa dose. RESULTS:Levodopa minimum plasma concentration (Cmin) for each levodopa/carbidopa dose and for the mean of all levodopa/carbidopa doses increased substantially with all active treatments (entacapone and opicapone) when compared to the control group (placebo), with values ranging from 1.7-fold (200 mg entacapone) to 3.3-fold (75 mg opicapone). No statistical difference was found for levodopa peak of systemic exposure (as assessed by maximum observed plasma concentration (Cmax)) between all active treatments and placebo. A significant increase in the levodopa extent of systemic exposure (as assessed by concentration-time curve (AUC)) occurred with all opicapone treatments in relation to placebo. No statistical difference was found for levodopa AUC when entacapone was compared to placebo. When compared to entacapone, both 50 and 75 mg opicapone presented a significant increase for the levodopa AUC. All active treatments significantly inhibited both peak (as assessed by Emax) and extent (as assessed by effect-time curve (AUEC)) of the COMT activity in relation to placebo. When compared to entacapone, all opicapone treatments significantly decreased the extent (AUEC) of the COMT activity due to a long-lasting and sustained effect. The tolerability profile was favorable for all active treatments. CONCLUSION:Opicapone, a novel third generation COMT inhibitor, when compared to entacapone, provides a superior response upon the bioavailability of levodopa associated to more pronounced, long-lasting, and sustained COMT inhibition. The tolerability profile was favorable. On the basis of the results presented in this study and along with the earlier pharmacology studies, it is anticipated that opicapone adjunct therapy at the dosages of 25 and 50 mg will provide an enhancement in levodopa availability that will translate into clinical benefit for Parkinson's disease patients.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Rocha JF,Falcão A,Santos A,Pinto R,Lopes N,Nunes T,Wright LC,Vaz-da-Silva M,Soares-da-Silva Pdoi
10.1007/s00228-014-1701-2subject
Has Abstractpub_date
2014-09-01 00:00:00pages
1059-71issue
9eissn
0031-6970issn
1432-1041journal_volume
70pub_type
杂志文章,随机对照试验abstract::The effects of a beta-blocker, carvedilol, on peripheral hemodynamics and hemorheologic parameters were evaluated in 11 geriatric patients with essential hypertension [3 men and 8 women aged 62-79 years (mean, 68.6 years)]. Carvedilol was given orally after breakfast at a dose of 10 or 20 mg daily for 8 weeks. Periphe...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF01409478
更新日期:1990-01-01 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:OBJECTIVE:The concentration of flecainide in hair was measured to determine its value as an index of individual drug-taking history. METHODS:Hair samples obtained from 15 patients treated with flecainide for more than 1 month were cut into 1-cm-long portions successively from its scalp end. The concentration of flecai...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:2002-05-01 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
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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...
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abstract::The efficacy of bopindolol and atenolol in the treatment of patients with chronic stable angina pectoris have been compared in a double blind, randomized study. Both bopindolol 1 mg and atenolol 100 mg for 6 weeks increased mean exercise time (25% and 22%, respectively, compared to placebo), time to angina (27% and 25...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1990-01-01 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
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abstract:OBJECTIVE:The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents. METHODS:A literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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abstract:OBJECTIVE:To determine the patterns of consumption in calcium channel blockers (CCB) groups in the Czech Republic between 1992 and 1999 and make a comparison with selected countries. METHODS:This was part of a drug utilization study using WHO methodology [Anatomical Therapeutic Chemical classification/defined daily do...
journal_title:European journal of clinical pharmacology
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doi:10.1007/s00228-002-0489-7
更新日期:2002-10-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-007-0272-x
更新日期:2007-05-01 00:00:00
abstract:AIM:To describe and evaluate spontaneous reports of suspected adverse reactions (ARs) associated with herbal laxatives received by the Italian Medicines Agency and the Italian National Institute of Health between April 2002 and January 2011. METHODS:Spontaneous reports of suspected ARs were individually analyzed by a ...
journal_title:European journal of clinical pharmacology
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doi:10.1007/s00228-011-1128-y
更新日期:2012-03-01 00:00:00
abstract:OBJECTIVES:An increased risk of all-cause and cardiovascular mortality in users of anxiolytic-hypnotic drugs (AHD) has been reported, and use of analgesics may be an additional factor. Therefore, we examined the association of AHD and analgesic use, alone and in combination, with all-cause and ischaemic heart disease (...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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abstract::Nicotine chewing gum (Nicorette 4 mg) and an identical placebo gum were administered on different days, in a double-blind cross over fashion, to 4 men, aged 25-52 years, and 4 women, aged 21-49 years, all healthy non-smokers. The subjects chewed the gum for 30 min and heart rate, blood pressure, electrocardiogram, fin...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00613610
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050446
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:European journal of clinical pharmacology
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doi:10.1007/s00228-009-0643-6
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journal_title:European journal of clinical pharmacology
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doi:10.1007/BF00613832
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abstract::The effect of menstrual cycle on the pharmacokinetics of theophylline has been studied in 9 female asthmatic patients. At three different times during the cycle (first, tenth and twentieth days) each subject received an i.v. infusion of 240 mg theophylline. Significant changes were found in the kinetics of theophyllin...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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abstract:PURPOSE:SPT-07A is an intravenous injection of (+)-2-borneol being developed for the treatment of acute ischemic stroke. This study aimed to investigate the pharmacokinetics, pharmacodynamics, safety, tolerability, and mass balance of SPT-07A after sequentially administered single and multiple infusions of SPT-07A at 1...
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00637683
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abstract::The anti-ischaemic properties of nimodipine 30 mg and 60 mg t.i.d. for 4 days has been tested in a double-blind, placebo-controlled, cross-over study based on the use of hyperventilation to reduce flow velocity in cerebral arteries. Whether the anti-ischaemic properties were due to a vasodilatator action on cerebral b...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1991-01-01 00:00:00
abstract::The pharmacokinetics of i.v. chloramphenicol succinate and oral chloramphenicol palmitate were studied in Ethiopian children with different nutritional states. In children with kwashiorkor the plasma clearance of chloramphenicol was significantly lower than in children of normal weight (4.16 ml/min/kg versus 7.53 ml/m...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00607094
更新日期:1983-01-01 00:00:00
abstract:OBJECTIVES:To evaluate zolpidem as a mechanism-based inactivator of human CYP3A in vitro, and to assess its metabolic interaction potential with CYP3A drugs (in vitro-in vivo extrapolation; IV-IVE). METHODS:A co- vs. pre-incubation strategy was used to quantify time-dependent inhibition of human liver microsomal (HLM)...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-009-0760-2
更新日期:2010-03-01 00:00:00
abstract:OBJECTIVE:Contraception is recommended for female patients during ursodeoxycholic acid (UDCA) treatment for the potential teratogenic effect of this bile acid, and the aim of our study was to determine whether this treatment affects the bioavailability of ethinylestradiol (EE2). METHODS:In this double-blind, randomise...
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/s00228-004-0796-2
更新日期:2004-09-01 00:00:00