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 corticosteroids, necessitating hospital admission for further management. Cysteinyl leukotrienes (LTs) are proinflammatory mediators that play an important role in systemic corticosteroids non-responsiveness. Montelukast is a potent LT-receptor antagonist, and an intravenous preparation caused rapid, sustained improvement of acute asthma exacerbations in adults. We hypothesized that a 30-mg dose of oral montelukast achieves peak plasma concentrations (Cmax ), comparable to the intravenous preparation (1700 ng/mL) and would be well tolerated in 15 children aged 5 to 12 years with acute asthma exacerbations. After administration of montelukast chewable tablets, blood samples were collected at 0, 15, 30, 45, 60, 120, 180, and 240 minutes. Plasma was separated and frozen at -80°C until analysis for montelukast concentration using liquid chromatography- tandem mass spectrometry. Median time to Cmax (tmax ) was 3.0 hours. Six participants (40%) achieved Cmax of 1700 ng/mL or higher. However, there was high interindividual variability in peak plasma concentration (median Cmax of 1378 ng/mL; range, 16-4895 ng/mL). No participant had side effects or adverse events. Plasma concentrations from this pilot study support the design of a weight-based dose-finding study aimed at selecting an optimal dose for future clinical trials to assess the efficacy of high-dose oral montelukast in children with moderate to severe asthma exacerbations.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Arnold DH,Van Driest SL,Reiss TF,King JC,Akers WSdoi
10.1002/jcph.1738subject
Has Abstractpub_date
2021-03-01 00:00:00pages
360-367issue
3eissn
0091-2700issn
1552-4604journal_volume
61pub_type
杂志文章abstract：:The pharmacokinetic characteristics of a slow-release formulation of clonidine (150 micrograms) were compared with those of a conventional formulation (75 micrograms) after acute and chronic (2 week) administration to 12 hypertensive subjects. The Tmax of the slow-release formulation was significantly later than for t...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1992.tb03858.x
更新日期：1992-05-01 00:00:00
abstract：:The efficacy of a eutectic mixture of local anesthetics (EMLA) in alleviating the pain associated with subcutaneous needle insertion for infusion of the iron-chelating agent, deferoxamine, was examined in 12 patients with homozygous beta-thalassemia. As reported by the patient using a 100-mm visual analogue scale, the...
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.1552-4604.1995.tb04062.x
更新日期：1995-03-01 00:00:00
abstract：:A vast and continuously growing amount of material on drugs exists in the literature to read and evaluate. Frequently, the papers and their recommendations are conflicting and contradictory. Readers are faced with the dilemma of deciding what to believe. The need for evidence-based medicine as a foundation for optimal...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：2002-09-01 00:00:00
abstract：:Moricizine, a unique Class I antiarrhythmic agent, was orally administered with and without a meal to 24 healthy male subjects to determine the effect of food on moricizine absorption and bioavailability. Relative to the fasting state, a standardized breakfast delayed the time to peak plasma moricizine concentration (...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1991.tb01912.x
更新日期：1991-09-01 00:00:00
abstract：:This study was performed to estimate the population pharmacokinetic (PK) parameters of etanercept in pediatric juvenile rheumatoid arthritis (JRA) patients and to compare the steady-state time-concentration profiles between etanercept 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly subcutaneous (SC) regimens by clini...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270004271945
更新日期：2005-03-01 00:00:00
abstract：:Angiotensin-converting enzyme inhibitors are effective at reducing blood pressure, whereas statins decrease plasma cholesterol impeding atherosclerosis. It is hypothesized that these medications may improve blood pressure and serum cholesterol by modifying the antioxidative status and energy metabolism of erythrocytes...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270009344854
更新日期：2010-02-01 00:00:00
abstract：:Droxicam is a nonsteroidal anti-inflammatory drug that is a pro-drug of piroxicam. The influence of concomitant administration of antacid or ranitidine on droxicam pharmacokinetics has been investigated. On three separate phases, 15 healthy volunteers received a single oral 20-mg dose of droxicam either alone, with an...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-12-01 00:00:00
abstract：:The effect of dose and gender on the pharmacokinetics (PK) and pharmacodynamics (PD) of zolpidem after administration of a buffered zolpidem sublingual tablet (ZST; Intermezzo®, Purdue Pharma L.P., Stamford, CT, USA) was evaluated in healthy non-elderly male and female volunteers. Subjects received a single morning do...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.220
更新日期：2014-03-01 00:00:00
abstract：:This 30-center, randomized, double-blind, placebo-controlled, parallel-group study was designed to (1) establish that 6.25 mg of hydrochlorothiazide (HCTZ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II (mild to moderate) systemi...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：10.1002/j.1552-4604.1995.tb05009.x
更新日期：1995-02-01 00:00:00
abstract：:The clinical pharmacist is an integral member of the Docent team at the University of Missouri--Kansas City School of Medicine with duties in both teaching and patient care. These doctoral-level clinical pharmacists have sole responsibility for providing instruction in basic pharmacology and pharmacokinetics and for t...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1981.tb05700.x
更新日期：1981-04-01 00:00:00
abstract：:To determine the elimination of high-molecular-weight hydroxyethyl starch (HES, Mw 450,000) in normal subjects, ten volunteers were given 500 ml 6% HES solution by intravenous infusion, and serial blood and urine samples were collected for nonglucose total carbohydrate determination. On the average, 46 and 64 per cent...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1982.tb02164.x
更新日期：1982-04-01 00:00:00
abstract：:Twenty-three normal volunteers who received morphine sulphate (MS Contin) with naltrexone completed this randomized, analytically blinded, two-way crossover comparison of the bioavailability of one 200-mg oral controlled-release morphine sulfate tablet with two 100-mg MSC tablets. Morphine effects were blocked by thre...
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.1552-4604.1995.tb04094.x
更新日期：1995-05-01 00:00:00
abstract：:A treatment gap exists for pediatric patients with renal impairment. Alterations in renal clearance and metabolism of drugs render standard dosage regimens inappropriate and may lead to drug toxicity, but these studies are not routinely conducted during drug development. The objective of this study was to examine the ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1676
更新日期：2020-12-01 00:00:00
abstract：:CPX-351, a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio, is approved in the United States for adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes. Population pharmacokinetics analyses were performed ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1366
更新日期：2019-05-01 00:00:00
abstract：:Cyclosporine (CsA) dosing is based on CsA plasma or blood concentrations measured 12 to 24 hours after drug administration (trough levels). This study evaluated the relationship between the timing of CsA concentrations and subsequent pharmacokinetic parameters to predict an optimal sampling period. Plasma samples were...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1992.tb03798.x
更新日期：1992-11-01 00:00:00
abstract：:The pharmacokinetics (PK), pharmacodynamics (PD), and safety of a platelet GPIIb/IIIa receptor antagonist, RGD891, and its active metabolite, RGD039, were evaluated after administration of various intravenous regimens of RGD891 to healthy male volunteers in two Phase I studies. Plasma and urine concentrations of RGD89...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：2000-11-01 00:00:00
abstract：:Weight loss has been associated with improvement in insulin sensitivity. It is consequently a cornerstone in the management of type 2 diabetes mellitus (T2DM). However, the strictly quantitative relationship between weight loss, insulin sensitivity, and clinically relevant glucose homeostasis biomarkers as well as cha...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1728
更新日期：2021-02-01 00:00:00
abstract：:The pharmacokinetics of enoximone and its sulfoxide metabolite were determined following administration of a single oral dose of 1 or 2 mg/kg in seven patients with congestive heart failure, and in two normal volunteers following a single 75-mg capsule, and were compared to those published previously. Plasma concentra...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1987.tb03083.x
更新日期：1987-09-01 00:00:00
abstract：:The enhanced nonenzymatic isomerization of pravastatin to SQ 31,906, a relatively inactive metabolite, has been demonstrated to occur on exposure to gastric acidity in humans. However, the effect of gastric metabolism on the pharmacodynamics of pravastatin has not been studied. In addition, it was hypothesized that so...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1998.tb04432.x
更新日期：1998-04-01 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：:A number of factors have been implicated in the interpatient variability of valproic acid (VPA) pharmacokinetics. These include patient age, concurrent anticonvulsant therapy, and dosage of VPA. In the clinical setting, it is important to determine which of these variables exert a major effect on the observed differen...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1985.tb02836.x
更新日期：1985-05-01 00:00:00
abstract：:The purpose of this study was to evaluate the pharmacokinetics of sulindac, a purported "renal sparing" nonsteroidal anti-inflammatory drug, and its effects on renal function and prostaglandin excretion in patients with reduced glomerular filtration rate. Twelve female patients (glomerular filtration rate 37 +/- 4 mL/...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03275.x
更新日期：1989-11-01 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：:In 14 patients with congestive heart failure (CHF) of various grade (NYHA class 2-4) the effects of zofenopril calcium (SQ 26,991) on blood pressure and forearm circulation were studied by venous occlusion plethysmography. Changes in plasma renin activity (PRA), aldosterone, Atrial natriuretic factor (ANF) and arginin...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1989.tb03282.x
更新日期：1989-12-01 00:00:00
abstract：:Although people living with human immunodeficiency virus and other comorbidities are expected to experience more grievous consequences with corona virus disease 2019 (COVID-19), recent cohort studies did not indicate this. Antiretrovirals (ARVs) might have a prophylactic role in these patients. The purpose of this stu...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1788
更新日期：2020-11-20 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：:Data from over 1000 patients with rheumatoid arthritis who received tolmetin sodium in double-blind and open studies have been pooled to assess long-term efficacy and safety. Duration of the studies was 12 weeks to 48 months. Mean age of patients was 54 years; ratio of males to females was 1:3. The results showed that...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1983.tb02739.x
更新日期：1983-07-01 00:00:00
abstract：:Quinaprilat is the active metabolite of quinapril, an orally active angiotensin-converting enzyme (ACE) inhibitor. The dose-response and duration-of-effect after single intravenous doses of quinaprilat and placebo (part A) and after administration of oral quinapril solution and intravenous quinaprilat (part B) were as...
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.1552-4604.1996.tb05028.x
更新日期：1996-05-01 00:00:00
abstract：:Azlocillin is an important acylureido penicillin antibiotic for the management of complex gram-negative infections particularly those caused by Pseudomonas species. The current studies demonstrate that it manifests dose-dependent pharmacokinetics during the usual regimens of clinical dosing, that enterohepatic recircu...
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.1552-4604.1987.tb03055.x
更新日期：1987-07-01 00:00:00
abstract：:Nine healthy subjects received 400 mg sodium valproate orally in the fasting state. Binding parameters of valproic acid to serum proteins were determined by Scatchard analysis for individual series of valproic acid data. Total and unbound (intrinsic) clearances (CLt and CLu) were calculated by dividing the dose by the...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb03932.x
更新日期：1993-02-01 00:00:00
