Abstract：
:The Cardiac Antiarrhythmic Suppression Trial (CAST) showed flecainide and encainide induced excess mortality compared with placebo. Labeling drugs as Class 1C is based on clinical observations, comprising measurements of the electrocardiographic parameters QRS. H-V and J-T intervals and of effective refractory period (ERP) as follows: 1--(QRS) wide, 2--(HV) long, 3--(ERP) unchanged, 4--(JT) unchanged. In vitro electrophysiology helped to explain the clinical findings. Flecainide and encainide rendered Na channels as nonconducting, but F and E were only slowly released from the channels after repolarization. At any given drug concentration, a proportion of total channels were eliminated, and the steady-state proportion increased at rising heart rate. It is not proven that the properties that lead to classification of a drug as 1C were those that caused excess deaths in the CAST. The proarrhythmic tendency of 1C drugs can be reduced by beta-blockade, and the mechanisms of adrenergic arrhythmogenicity are discussed. Propafenone is both a 1C drug and a beta-blocker, and its pharmacologic profile is reviewed to illustrate how it resembles and differs from flecainide and encainide. Some features of the CAST are assessed with particular reference to the extent to which conclusions drawn from the results may be justifiably extrapolated to other drugs classified as 1C.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Vaughan Williams EMdoi
10.1002/j.1552-4604.1991.tb03695.xsubject
Has Abstractpub_date
1991-02-01 00:00:00pages
123-35issue
2eissn
0091-2700issn
1552-4604journal_volume
31pub_type
杂志文章,评审abstract：:The purpose of this open-label, parallel-group study was to investigate the effect of severe renal impairment on the pharmacokinetics (PK), tolerability, and safety of clazosentan, an intravenous endothelin receptor antagonist. Clazosentan was administered as a continuous intravenous infusion of 1 mg/h for a period of...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270010368975
更新日期：2011-03-01 00:00:00
abstract：:The authors examined the pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in 17 patients (4 children, 13 adults) with B-lineage lymphoid malignancies, including 12 patients with acute lymphoblastic leukemia (ALL) and 5 patients with non-Hodgkin's lymphoma (NHL). The immunoconjugat...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/00912709922012051
更新日期：1999-12-01 00:00:00
abstract：:Nicotinic acid is a water-soluble B-complex vitamin that has been shown, in high doses, to lower total plasma cholesterol (C), LDL-C, and VLDL-triglycerides (Tg), while raising HDL-C in patients with type II, III, IV, and V hyperlipoproteinemia. Its exact mechanism of action is not known, but it appears to lower the p...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1991.tb03750.x
更新日期：1991-07-01 00:00:00
abstract：:The primary objective was to determine the pharmacokinetics of single oral and intravenous doses of pantoprazole in children 2 to 16 years of age. The secondary objective was to assess the safety and tolerability of these doses. Male and female hospitalized and nonhospitalized patients from ages 5 to 16 years received...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1177/0091270008321811
更新日期：2008-11-01 00:00:00
abstract：:Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, approved for second-line therapy for advanced renal cell carcinoma (RCC). Axitinib population pharmacokinetic and pharmacokinetic/pharmacodynamic relationships were evaluated. Using nonlinear mixed effects modelin...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.73
更新日期：2013-05-01 00:00:00
abstract：:After space-flights of less than ten days, orthostatic hypotension upon reentry is characterized by plasma volume depletion that may lead to activation of the Bezold-Jarisch reflex which is also considered to be the mechanism of vasovagal (neurocardiogenic) syncope. For space-flight of longer duration, loss of cardiov...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1994.tb04988.x
更新日期：1994-05-01 00:00:00
abstract：:Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faste...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.391
更新日期：2015-02-01 00:00:00
abstract：:The approved antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate, were considered good candidates for a fixed-dose combination product that could be administered as a single pill once daily (qd), thereby simplifying existing treatment regimens and promoting patient adherence. As both drugs are extens...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270007300951
更新日期：2007-06-01 00:00:00
abstract：:This multicenter, open-label study evaluated the effects of multiple doses of peginterferon alfa-2b on the steadystate pharmacokinetics of methadone in 20 adults with hepatitis C virus infection who were enrolled in a methadone maintenance program. All subjects received peginterferon alfa-2b 1.5 mug/kg/wk for 4 weeks ...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1177/0091270007299760
更新日期：2007-05-01 00:00:00
abstract：:Direct comparisons of the pharmacokinetic (PK) and systemic pharmacodynamic (PD) properties of inhaled corticosteroids after single and multiple dosing in the same subjects are scarce. The objective of this study was to compare thePK/PDproperties of clinically equivalent, single, and multiple doses of dry-powder formu...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/00912700122012913
更新日期：2001-12-01 00:00:00
abstract：:A novel, nonscrotal, transdermal delivery system for testosterone therapy has been marketed for treatment of hypogonadal men. The usual dose of this system is two 2.5 mg/day systems applied daily. A new system has been developed that administers a dose of 5 mg/day using a single patch rather than two patches. A random...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/j.1552-4604.1998.tb04377.x
更新日期：1998-01-01 00:00:00
abstract：:Pain is a troublesome nonmotor symptom of Parkinson's disease (PD). This double-blind exploratory pilot study (NCT01744496) was the first to specifically investigate the effect of a dopamine agonist on PD-associated pain as primary outcome. Patients with advanced PD (ie, receiving levodopa) and at least moderate PD-as...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1002/jcph.678
更新日期：2016-07-01 00:00:00
abstract：:Blood concentrations of cyclosporine were determined in adult and pediatric patients following orthotopic liver transplantation to quantitate cyclosporine blood clearance and oral absorption. Seventeen bioavailability studies were performed following transplantation surgery in nine children and seven adults. The intra...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1986.tb02966.x
更新日期：1986-11-01 00:00:00
abstract：:The most thorough and clinically relevant approach to hypnotic drug evaluation is one that balances the strengths and weaknesses of clinical trials and sleep laboratory evaluations. Advantages of clinical trials include the ability to evaluate large numbers of subjects and specific target groups and to thoroughly asse...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,评审
doi：10.1002/j.1552-4604.1979.tb02489.x
更新日期：1979-07-01 00:00:00
abstract：:In this study, the authors assessed the bioequivalence of two fluoxetine tablet formulations in 24 healthy volunteers of both sexes who received a single 20 mg dose of each fluoxetine formulation, and a new sensitive method for the quantification of fluoxetine and norfluoxetine in human plasma was developed. The study...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/00912709922011827
更新日期：1999-10-01 00:00:00
abstract：:Propiverine extended release is expected to be better tolerated compared to immediate release tablets because of slower drug release and reduced formation of active metabolites in the colon. CYP3A4 and ABCC2, the major variables in pharmacokinetics of propiverine, are less expressed in the colon. Therefore, dispositio...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270008315314
更新日期：2008-05-01 00:00:00
abstract：:A randomized, single-blind, placebo-controlled, parallel-group study was conducted to assess the effect of age and gender on the pharmacokinetics and pharmacodynamics of rivaroxaban - an oral, direct Factor Xa inhibitor. Subjects (n = 34) were enrolled into four groups: young males or females (aged 18-45 years) and el...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.5
更新日期：2013-03-01 00:00:00
abstract：:Categorizations of best response observed at week 8 (between week 3 and 14) of first-line treatment in two studies of bevacizumab plus chemotherapy in Western (878 patients) and Chinese (198 patients) patients with non-small cell lung cancer were assessed together with baseline prognostic factors in multivariate param...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.191
更新日期：2014-03-01 00:00:00
abstract：:The efficacy of intravenously administered metoprolol, a cardioselective beta-adrenergic blocking agent, was evaluated in the treatment of supraventricular tachyarrhythmias in 16 patients. The arrhythmias that were treated were atrial fibrillation (11 patients), atrial flutter (2 patients), supraventricular tachycardi...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1991.tb03765.x
更新日期：1991-08-01 00:00:00
abstract：:Pentoxifylline, a nonselective phosphodiesterase inhibitor, has immunomodulatory activity in vitro and in vivo and potentiates the suppressive effects of glucocorticoids and cyclosporine on lymphocyte proliferation in vitro. Since phosphodiesterase isotypes 3 and 4 predominate in lymphocytes, the authors measured the ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/00912709922008443
更新日期：1999-08-01 00:00:00
abstract：:A single blind crossover study with washout phases showed that pyrazinoylguanidine (PZG) reduced elevated serum concentrations of urea, triglycerides, and cholesterol in patients with renal insufficiency. Pyrazinoylguanidine was saluretic, without affecting serum potassium or glucose concentrations. The onset of PZG's...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb04703.x
更新日期：1993-06-01 00:00:00
abstract：:The acute bronchomotor effect of nabilone, a synthetic cannabinoid compound, was compared to that of terbutaline sulfate and placebo in six healthy and six asthmatic subjects. Bronchodilation following nabilone was intermediate between that of terbutaline and placebo in the healthy subjects but was equivalent to place...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1983.tb02715.x
更新日期：1983-04-01 00:00:00
abstract：:For more than a decade, first responders and the general public have been able to treat suspected opioid overdoses using an improvised nasal naloxone device (INND) constructed from a prefilled syringe containing 2 mg of naloxone (1 mg/mL) attached to a mucosal atomization device. In recent years, the U.S. Food and Dru...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.1401
更新日期：2019-08-01 00:00:00
abstract：:The effects of long-term triple drug therapy on renal function in patients with moderate to severe essential hypertension have not been evaluated systematically. We prospectively studied fifteen male patients with moderate to severe essential hypertension receiving triple drug therapy (metolazone, atenolol or betaxolo...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03423.x
更新日期：1989-09-01 00:00:00
abstract：:Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subj...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.302
更新日期：2014-09-01 00:00:00
abstract：:Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patient...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1508
更新日期：2020-01-01 00:00:00
abstract：:Clinical pharmacology of L-asparaginase was compared by intramuscular and intravenous injections in 12 patients with metastatic cancer or leukemia. Following a single intramuscular injection at the gluteal site of L-asparaginase (10,000 IU/m2), the enzyme appeared in plasma as measured initially at 1 hour, but plateau...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb01752.x
更新日期：1981-02-01 00:00:00
abstract：:The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) were evaluated, with 22 subjects receiving enzastaurin. The mean half-lives of enzastaurin and it...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270007304775
更新日期：2007-09-01 00:00:00
abstract：:The integrated minimal model allows assessment of clinical diagnosis indices, for example, insulin sensitivity (SI ) and glucose effectiveness (SG ), from data of the insulin-modified intravenous glucose tolerance test (IVGTT), which is laborious with an intense sampling schedule, up to 32 samples. The aim of this stu...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1707
更新日期：2021-01-01 00:00:00
abstract：:The aim of this study was to test the usefulness of the metabolite/caffeine ratio for the evaluation of hepatic dysfunction. Subjects with liver cirrhosis and chronic hepatitis, as well as healthy volunteers, were given the oral dose of 300 mg caffeine. Blood samples were collected after 4, 8, and 12 hours. Concentrat...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004263468
更新日期：2004-04-01 00:00:00
