Abstract:
:To compare the steady-state kinetic profiles and ectopy-suppression rates of two sustained-release forms of quinidine with those of a conventional quinidine preparation, 18 patients with ventricular ectopy were studied in randomized crossover fashion. The drugs were conventional quinidine sulfate 300 mg q6h, sustained-release quinidine sulfate 600 mg q12h, and sustained-release quinidine gluconate 648 mg q12h. Following baseline electrocardiographic ambulatory monitoring, each drug was given for three days, with repeat ambulatory monitoring and serial plasma drug level determinations performed on the third day. There were no washout periods between treatments. Plasma quinidine levels were assayed by both enzyme multiplied immunoassay technique (EMIT) and quinidine-specific high-performance liquid chromatography (HPLC) methods. Using actual steady-state HPLC values, there were no differences in the area under the plasma concentration-time curve (AUC) among the three treatments; the dose-corrected AUC was greater for quinidine gluconate than for the other two preparations. Using EMIT values, mean plasma quinidine levels from the conventional quinidine sulfate regimen were greater during the last five hours of the 12-hour study interval. A consistently strong inverse relationship between EMIT plasma quinidine levels and hourly ectopy rates was present in only one of eight (13%) responders. Diurnal variation of quinidine kinetics was observed after two days of each treatment; trough values at midnight were slightly lower than trough values at noon. Among patients demonstrating at least 70% suppression of premature ventricular contractions (PVCs), there were no differences in ectopy rates or ectopy-suppression rates among treatments. Dosing sustained-release quinidine sulfate 600 mg or quinidine gluconate 648 mg q12h was clinically acceptable in the small number of responders studied.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Lehmann CR,Boran KJ,Kruyer WB,Van Reet RE,Scoville GS,Pierson WP,Melikian AP,Crowe JT,Wright GJdoi
10.1002/j.1552-4604.1986.tb02956.xsubject
Has Abstractpub_date
1986-11-01 00:00:00pages
598-604issue
8eissn
0091-2700issn
1552-4604journal_volume
26pub_type
临床试验,杂志文章,随机对照试验abstract::We aim to evaluate the influence of covariates, including cytochrome P450 3A (CYP3A) genetic polymorphisms, on the pharmacokinetics of midazolam (MDZ) in Asian cancer patients, using a population pharmacokinetic approach. Pharmacokinetic data were obtained from 24 adult cancer patients who received an intravenous bolu...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/jcph.230
更新日期:2014-02-01 00:00:00
abstract::A randomized, double-blind, within-patient, crossover study was carried out after bilateral "identical" surgical procedures using local anesthesia only. A 3-day tablet regime of racemic ketoprofen 75 mg or acetaminophen 1000 mg qid (x 4) was given starting 3 hours after surgery. Ketoprofen reduced objectively measured...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/0091270002250603
更新日期:2003-03-01 00:00:00
abstract::The population pharmacokinetics of desmopressin in children with nocturnal enuresis and in healthy adults were compared using a 1-compartment model with first-order absorption and first-order elimination. In addition, the model consisted of a number of transit compartments before absorption to describe a lag-time. The...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1177/0091270006291838
更新日期:2006-10-01 00:00:00
abstract::Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, ty...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1045
更新日期:2018-04-01 00:00:00
abstract::Twelve patients chronically maintained on warfarin were administered 80 mg atorvastatin for 2 weeks. Mean prothrombin times decreased slightly, but only for the first few days of the two-week treatment period. Thus atorvastatin had no consistent effect on the anticoagulant activity of warfarin and adjustment in warfar...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1997.tb04288.x
更新日期:1997-11-01 00:00:00
abstract::The effect of telbivudine on cardiac repolarization was evaluated in healthy participants at clinical and supratherapeutic doses. Sixty-two participants were enrolled, stratified by sex, and randomized according to a crossover design among 4 treatment sequences: placebo, a single moxifloxacin 400-mg dose as positive c...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270009337943
更新日期:2009-12-01 00:00:00
abstract::The pharmacokinetics, pharmacodynamics, and safety of the marketed formulation of microencapsulated octreotide acetate were evaluated in an open-label study in 22 healthy cholecystectomized subjects. Each subject received a single 30 mg dose of microencapsulated octreotide acetate intramuscularly (i.m.). Concentration...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1177/00912700022009242
更新日期:2000-05-01 00:00:00
abstract::In the Phase I study, the new anthracycline aclacinomycin A was given to 22 advanced cancer patients on a schedule of daily intravenous administration for five days repeated every four weeks. The limiting toxicity was myelosuppression, which was severe at a dose of 30 mg/m2 per day for five days. Platelet nadirs were ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1982.tb02686.x
更新日期:1982-08-01 00:00:00
abstract::The pharmacokinetic actions, bioequivalence, and cardiovascular effects of two verapamil products were studied in a randomized, double-blind, crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate-release verapamil in 120-mg twice-daily...
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.1552-4604.1997.tb04331.x
更新日期:1997-06-01 00:00:00
abstract::The selective T-cell costimulation modulator abatacept is approved for treatment of adult rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA; 6-17 years [intravenous] and 2-17 years [subcutaneous]). An extrapolation approach was taken to determine subcutaneous weight-tiered doses of abatac...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1797
更新日期:2020-12-07 00:00:00
abstract::MC4-NN2-0453 is a novel, long-acting, selective, melanocortin-4-receptor agonist developed for treatment of obesity. This first-human-dose, randomized, double-blind, placebo-controlled trial investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of MC4-NN2-0453 in ov...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1002/jcph.211
更新日期:2014-04-01 00:00:00
abstract::The half-life of amikacin in serum has been measured following the administration of a single intravenous injection of 7 mg/kg in nine adult patients with varying degrees of renal function impairment and in four patients with normal renal function. A linear relationship between the half-life and the serum concentratio...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1975.tb05924.x
更新日期:1975-10-01 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::Using a sensitive and specific radioimmunoassay the pharmacokinetic disposition of clonidine was determined in hypertensive patients after a single dose and then after 5, 28 and 56 days of chronic dosing with 75 micrograms bd. Following a single dose of clonidine maximal plasma concentrations of 0.34 +/- 0.06 ng/ml we...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1989.tb03335.x
更新日期:1989-04-01 00:00:00
abstract::To evaluate the population pharmacokinetics of valproic acid in children, 97 steady-state serum valproate concentration measurements were gathered during normal, routine, outpatient care of 52 children with epilepsy (1.2-16 years of age). Levels were obtained from patients receiving valproate monotherapy (49%) or valp...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1995.tb04020.x
更新日期:1995-10-01 00:00:00
abstract::The centrally acting agents are one of several differing classes of drugs now available for antihypertensive therapy. The availability of newer pharmacologic classes, including the beta-blockers, alpha-blockers. ACE inhibitors and calcium channel blockers, has resulted in a relative decline in the use of the centrally...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1002/j.1552-4604.1989.tb03387.x
更新日期:1989-07-01 00:00:00
abstract::Retigabine, a first-in-class selective M-current potassium channel opener, is a novel antiepileptic compound currently in clinical development. The purpose of this randomized placebo-controlled study was to assess retigabine oral safety and pharmacokinetics in healthy male volunteers (N = 45). Subjects received one do...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1177/00912700222011210
更新日期:2002-02-01 00:00:00
abstract::Acute asthma exacerbations are primarily due to airway inflammation and remain one of the most frequent reasons for childhood hospitalizations. Although systemic corticosteroids remain the mainstay of therapy because of their anti-inflammatory properties, not all inflammatory pathways are responsive to systemic cortic...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1738
更新日期:2021-03-01 00:00:00
abstract::Clinical investigations using isoform-selective probes to phenotype cytochrome P450 activity and interaction studies using isoform-selective inhibitors to determine P450 involvement in drug metabolism assume minimal interday variability in P450 activity. CYP3A4 is the most abundant human P450 isoform and metabolizes a...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1177/00912709922008290
更新日期:1999-07-01 00:00:00
abstract::Four protease inhibitor antiviral agents (ritonavir, indinavir, nelfinavir, saquinavir) were evaluated as in vitro inhibitors of the activity of six human cytochromes using an in vitro model based on human liver microsomes. Ritonavir was a highly potent inhibitor of P450-3A activity (triazolam hydroxylation), having i...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/j.1552-4604.1998.tb04398.x
更新日期:1998-02-01 00:00:00
abstract::Twenty young (45 years or younger) and 20 older (55 years or older) adult patients with mild hypertension were enrolled in this study to compare the hemodynamic effects of labetalol versus placebo in two age groups. Ten patients in each group were randomly assigned to receive either a single oral dose of labetalol (20...
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.1552-4604.1988.tb03153.x
更新日期:1988-04-01 00:00:00
abstract::This study outlines the attempts of four states (Louisiana, Kansas, Wisconsin, and Michigan) to restrict anorectic prescriptions. The actions in these four states exemplify the various mechanisms used in regulating anorectics, ranging from educational efforts to legislative enactments. We examine the evidence used in ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1988-05-01 00:00:00
abstract::Recent advances in in vitro metabolism methods have led to an improved ability to predict clinically relevant metabolic drug-drug interactions. To address the relationships of in vitro metabolism data and in vivo metabolism outcomes, the Office of Clinical Pharmacology and Biopharmaceutics in the Center for Drug Evalu...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1177/00912709922008515
更新日期:1999-09-01 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::Recently, a new latanoprost ophthalmic solution containing cyclodextrins was developed. The purpose of the present work was to compare the stability, clinical efficacy, and adverse effect profile of this formulation with the innovator product. The innovator formulation was stable at 4 degrees C but exhibited degradati...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1177/0091270006292626
更新日期:2007-01-01 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::Sitagliptin is an orally active, highly selective dipeptidyl peptidase IV (DPP-4) inhibitor for treatment of type 2 diabetes mellitus. This randomized, open-label, 2-part, 2-period crossover study assessed pharmacokinetics/pharmacodynamics of warfarin in the presence/absence of multiple-dose sitagliptin. Twelve partic...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1177/0091270009341653
更新日期:2009-10-01 00:00:00
abstract::Cyclophosphamide-based regimens are front-line treatment for numerous pediatric malignancies; however, current dosing methods result in considerable interpatient variability in tumor response and toxicity. In this pediatric population, the authors' objectives were (1) to quantify and explain the pharmacokinetic variab...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1177/0091270008325928
更新日期:2009-01-01 00:00:00
abstract::The incidence of migraine is higher among women than men and peaks during the reproductive years, when contraceptive medication use is common. Atogepant, a potent, selective antagonist of the calcitonin gene-related peptide receptor-in development for migraine prevention-is thus likely to be used by women taking oral ...
journal_title:Journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1002/jcph.1610
更新日期:2020-09-01 00:00:00
abstract::Data from 58 premarketing studies of the nonsteroidal antiinflammatory drug flurbiprofen were pooled for analyses of adverse drug reactions (ADRs). These studies included 5602 patients treated with flurbiprofen (N = 4123), aspirin (N = 1033), or placebo (N = 446) for varying durations. Diagnoses included rheumatoid ar...
journal_title:Journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1002/j.1552-4604.1990.tb03604.x
更新日期:1990-04-01 00:00:00