Abstract：
:Effective drug therapy to optimally influence disease requires an understanding of a drug's pharmacokinetic, pharmacodynamic, and pharmacogenomic interrelationships. In pediatrics, age is a continuum that can and does add variability in drug disposition and effect. This article addresses the many important factors that influence drug disposition and effect relative to age. What is known about the influence of maturation on the processes of drug absorption, distribution, metabolism, excretion, and drug receptor dynamics are outlined. Our state of understanding of many of these factors remains in flux, however, and only with additional study will we be able to better anticipate and model drug-response relationships across the age continuum. Being able to continuously improve our care of the ill pediatric patient while simultaneously being able to accurately determine the utility of new drugs and chemical entities in this population requires our enhanced understanding of these disposition characteristics.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
van den Anker J,Reed MD,Allegaert K,Kearns GLdoi
10.1002/jcph.1284subject
Has Abstractpub_date
2018-10-01 00:00:00pages
S10-S25eissn
0091-2700issn
1552-4604journal_volume
58 Suppl 10pub_type
杂志文章,评审abstract：:The pharmacokinetics of codeine, codeine glucuronide, morphine, and morphine glucuronide were assessed after single- (60 mg) and multiple-dose (60 mg every six hours for nine doses) oral administration of codeine sulfate to six normal volunteers. Multiple blood and urine samples were collected after administration of ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1987.tb05601.x
更新日期：1987-12-01 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 evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of a novel depot formulation of abarelix, a new gonadotropin-releasing hormone (GnRH) antagonist. This was an open-label, sequential two-phase study in healthy male subjects ages 50 to 75. Subjects received a single intramuscular (IM) do...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004264920
更新日期：2004-05-01 00:00:00
abstract：:DS-1040, a low-molecular-weight imidazole derivative, inhibits the enzymatic activity of thrombin-activatable fibrinolysis inhibitor (TAFIa), enhancing endogenous tissue plasminogen activator-triggered fibrinolysis. This first-in-human, randomized, placebo-controlled, phase 1 study evaluated the safety, pharmacokineti...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.1474
更新日期：2019-12-01 00:00:00
abstract：:A bioequivalence study of two oral formulations of 300 mg ranitidine was carried out in 16 healthy volunteers (8 men and 8 women), and the pharmacokinetics in both sexes were compared. There was bioequivalence of both formulations. The terminal half-life of ranitidine was 7% shorter and the oral apparent clearance 10....
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.tb04245.x
更新日期：1996-08-01 00:00:00
abstract：:Recent initiatives calling for changes in medical education, such as the General Professional Education of the Physician and Robert Wood Johnson Reports, have recommended alternative teaching approaches to the lecture format. The Patient-Oriented Problem-Solving (POPS) exercises, sponsored by the Upjohn Company (Kalam...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1995.tb04999.x
更新日期：1995-02-01 00:00:00
abstract：:The relationship between indenolol (an investigational agent) plasma levels and the drug's effect on blood pressure and heart rate was investigated after single and repeated once daily administration at two dosage levels (60 mg and 120 mg) in two different groups of patients with first or second stage hypertension, ac...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1985.tb02851.x
更新日期：1985-07-01 00:00:00
abstract：:There is an increasing interest in the simultaneous administration of several probe substrates to characterize the activity of multiple drug-metabolizing enzymes, the so-called "cocktail" approach. However, this method remains controversial and is being investigated more extensively. No general consensus has emerged o...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270003261333
更新日期：2004-02-01 00:00:00
abstract：:The contribution of renal and non-renal clearance toward targeted concentrations and/or effects of therapeutic proteins in nephrotic patients are unknown. This study dissected the contribution of clearance pathways to adalimumab elimination in patients with focal segmental glomerulosclerosis (FSGS). Urine was collecte...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.121
更新日期：2013-09-01 00:00:00
abstract：:A pediatric population pharmacokinetic model including covariate effects was developed using data from 2 clinical trials in pediatric patients with epilepsy (SP0847 and SP1047). Lacosamide plasma concentration-time data (n = 402) were available from 79 children with body weights ranging from 6 to 76 kg, and a balanced...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1340
更新日期：2019-04-01 00:00:00
abstract：:Tissue pharmacokinetics and plasma protein binding of colistin have not been described in humans in vivo. Colistin concentrations in plasma, muscle, and subcutis of healthy volunteers were measured by microdialysis after a single dose of 2.5 million IU of colistin methanesulfonate. In vitro microdialysis experiments a...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/jcph.419
更新日期：2015-04-01 00:00:00
abstract：:Forty-two healthy Caucasian subjects were randomized in a double-blind, parallel three-group study (14 subjects per group) to investigate potential electrocardiographic and pharmacokinetic interactions between the antimalarials artemether-lumefantrine (six-dose regimen of Riamet over 3 days) and quinine (2-h intraveno...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/009127002401382632
更新日期：2002-10-01 00:00:00
abstract：:The most recent International Conference on Harmonisation E14 Q&A document states that a separate positive control would not be necessary provided sufficiently high exposures are achieved in the early-phase studies. Realistically, a phase 1 study is unlikely to include a pharmacological positive control, and in cases ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.975
更新日期：2018-01-01 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：:The impact of a microgravity simulation using a head-down tilt (-6 degrees) on lidocaine pharmacokinetics used as a probe to evaluate hepatic blood flow is discussed. Eight healthy male subjects were selected for a 7-day study, including a 4-day head-down tilt from day 2 to day 5. Subjects were given 1 mg/kg of lidoca...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1995.tb04110.x
更新日期：1995-07-01 00:00:00
abstract：:Nineteenth century ophthalmology, characterized by significant gains in diagnostic techniques, provided the basis for great advancements in treatment during the 20th century. Drug therapy at the turn of the century was empiric, palliative, and often toxic. The development of ocular pharmacology during the 20th century...
journal_title：Journal of clinical pharmacology
pub_type： 历史文章,杂志文章
doi：10.1177/00912700022009710
更新日期：2000-09-01 00:00:00
abstract：:Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor and an inhibitor of UDP-glucuronosyltransferase-1A1 (UGT1A1), which is involved in raltegravir clearance. Raltegravir, an HIV integrase inhibitor, may be used in combination with HCV treatment in HCV/HIV co-infected patients. In this open-label,...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.418
更新日期：2015-04-01 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：:This double-blind, parallel-group study was performed at a single site in patients with moderate or severe pain after oral surgery to remove one or more impacted third molars. Patients recorded their pain intensity at baseline and were then assigned to receive a single dose of bromfenac sodium (25 mg or 50 mg), tramad...
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.tb04453.x
更新日期：1998-05-01 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 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：:The type II histamine receptor antagonists, cimetidine and ranitidine, widely used in treatment of peptic ulcer disease have been reported to cause bradycardia. To evaluate the cardiovascular effects of H2 antagonists nineteen healthy volunteers were entered into a double-blind crossover comparison of cimetidine 300 m...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1989.tb03365.x
更新日期：1989-05-01 00:00:00
abstract：:Varenicline is a novel selective α4β2 nicotinic acetylcholine partial agonist developed for smoking cessation. Single- and multiple dose studies were conducted to investigate pharmacokinetics, safety, and tolerability of varenicline in healthy male Japanese smokers. The single-dose study was conducted as a double-blin...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1177/0091270010372388
更新日期：2011-04-01 00:00:00
abstract：:It is well known that the CYP2C19 genetic polymorphism influences the pharmacokinetics and pharmacodynamics of proton pump inhibitors (PPIs), but no report has addressed the effects on ilaprazole, a newly developed PPI. To investigate the effects of the CYP2C19 genetic polymorphism on the disposition and pharmacodynam...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270011408611
更新日期：2012-07-01 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：:The interactive effects of the coadministration of steady-state cimetidine and single-dose pentopril, an angiotensin converting enzyme inhibitor, on the pharmacokinetic disposition of each other were studied in humans. Cimetidine reduced the clearance of pentopril by 11 to 14%. This reduction in clearance was shown to...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03136.x
更新日期：1988-03-01 00:00:00
abstract：:Inhaled glucocorticoids induce therapeutic and adverse systemic effects via the same types of receptors. Analysis of the pharmacokinetic/pharmacodynamic parameters of inhaled glucocorticoids generates a risk-benefit value (RBV). Targeted efficacy with minimal adverse effects helps to quantify an appropriate RBV. High ...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1177/0091270003260334
更新日期：2004-01-01 00:00:00
abstract：:The aim of this pharmacokinetic analysis was to develop and validate a population pharmacokinetic model for R- and S-ibuprofen from samples obtained after 3 successive administrations of ibuprofen (10-5-5 mg/kg) at 24-hour intervals to preterm newborn infants aged from <6 hours to 8 days of life. A model including uni...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270008323752
更新日期：2008-12-01 00:00:00
abstract：:Ofatumumab is a human monoclonal antibody that binds to a unique CD20 epitope on the surface of B lymphocytes, resulting in efficient lysis of CD20-expressing cells via complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. The potential effect of ofatumumab on cardiac repolarization and ...
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.376
更新日期：2015-01-01 00:00:00
abstract：:The efficacy and safety of esmolol, a titratable intravenous beta-adrenergic blocking agent with a short elimination half-life (t 1/2 = 9.0 min) was evaluated in a multicenter open-label study for the treatment of supraventricular tachyarrhythmias (heart rate greater than 100 bpm). The study also investigated the feas...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03209.x
更新日期：1988-08-01 00:00:00
