Abstract：
:Nilotinib, an oral inhibitor of the tyrosine kinase activity of Abelson protein, is approved for the treatment of patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase and patients with CML in chronic phase or accelerated phase resistant or intolerant to prior therapies. This review describes the pharmacokinetic and pharmacodynamic data of nilotinib in patients with CML and in healthy volunteers. Nilotinib is rapidly absorbed, with a peak serum concentration approximately 3 hours after dosing. The area under the plasma drug concentration-time curve over 24 hours and the peak serum concentration of nilotinib were dose proportional from 50-400 mg once daily. The metabolism of nilotinib is primarily via hepatic cytochrome P450 (CYP) 3A4 according to in vitro studies. In the clinical setting, exposure to nilotinib was significantly reduced by the induction of CYP3A4 with rifampicin and significantly increased by the inhibition of CYP3A with ketoconazole. Additionally, nilotinib is a competitive inhibitor of CYP3A4/5, CYP2C8, CYP2C9, CYP2D6, and uridine diphosphate glucuronosyltransferase 1A1. The bioavailability of nilotinib is increased by up to 82% when given with a high-fat meal compared with fasted state. There is a positive correlation between the occurrences of all-grade total bilirubin elevations and the steady-state nilotinib trough concentrations. Fredericia method corrected QT interval change from baseline was observed to have a correlation with nilotinib exposure. No significant relationship between nilotinib exposure and major molecular response at 12 months was seen at therapeutic doses of nilotinib 300-400 mg, probably due to the narrow range of the doses investigated.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Tian X,Zhang H,Heimbach T,He H,Buchbinder A,Aghoghovbia M,Hourcade-Potelleret Fdoi
10.1002/jcph.1312subject
Has Abstractpub_date
2018-12-01 00:00:00pages
1533-1540issue
12eissn
0091-2700issn
1552-4604journal_volume
58pub_type
杂志文章,评审abstract：:The influence of food on the bioavailability of trimoprostil , a new antiulcer prostaglandin E2 derivative, was investigated in healthy male volunteers in four separate studies. Doses of 0.75, 1.5, and 3.0 mg were administered orally in both the presence and absence of food followed by serial blood sampling through 24...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1984.tb01830.x
更新日期：1984-04-01 00:00:00
abstract：:The frequency of hemodialysis-associated hemorrhage was studied prospectively in two successive, parallel, heparin-controlled studies using epoprostenol (PGI2; average dose, 4.1 ng/kg.min) as the sole antithrombotic agent. Sixty-three patients with active or recently active bleeding underwent 163 hemodialysis treatmen...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1988.tb03222.x
更新日期：1988-09-01 00:00:00
abstract：:In the pivotal TEMPO 3:4 trial, the arginine vasopressin V2-receptor antagonist tolvaptan reduced the rate of kidney growth in patients with autosomal dominant polycystic kidney disease. Tolvaptan was initiated as daily morning/afternoon doses of 45/15 mg, and uptitrated weekly to 60/30 mg and 90/30 mg according to pa...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1002/jcph.880
更新日期：2017-07-01 00:00:00
abstract：:The effect of the proton pump inhibitor dexlansoprazole, an enantiomer of lansoprazole, on QT intervals was assessed after oral administration of a modified-release formulation of dexlansoprazole (dexlansoprazole MR). In this randomized, positive-comparator, placebo-controlled, 4-period crossover study, 40 healthy par...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/0091270009339188
更新日期：2009-12-01 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：:Glasdegib is approved for treating acute myeloid leukemia in elderly patients at 100 mg once daily in combination with low-dose cytarabine. Exposure-efficacy analysis showed that the survival benefit of glasdegib was not glasdegib exposure-dependent. The relationship between glasdegib exposure and adverse event (AE) c...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.1742
更新日期：2021-03-01 00:00:00
abstract：:The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is difficult because symptoms are seldom pathognomonic. The authors compared the performance of two new diagnostic aids in the differential diagnosis of 27 cases of skin reactions associated with sulfonamide therapy. One test, the Bayesian Adver...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1994.tb04736.x
更新日期：1994-12-01 00:00:00
abstract：:The effect of food on the oral bioavailability of sustained-release morphine sulfate tablets (ORAMORPH SR; Roxane Laboratories, Inc., Columbus, OH; OSR) was examined in an open-label, randomized, two-period crossover study. Healthy male volunteers received a 30-mg OSR tablet orally every 12 hours for seven doses durin...
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.1552-4604.1992.tb03802.x
更新日期：1992-11-01 00:00:00
abstract：:L- and T-type voltage-dependent transmembrane calcium channels are important for normal functioning of the cardiovascular system. T-type channels are a heterogeneous group, and have physiologic and pathophysiologic relevance in a number of organ systems, including the heart and central nervous system. They appear to b...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1998.tb04804.x
更新日期：1998-08-01 00:00:00
abstract：:This study further characterized the impact of concentration-dependent protein binding on the bioavailability and clinical use of the immediate-release (IR) and controlled-release (CR) dosage forms of disopyramide after single doses and during steady-state conditions in ten healthy volunteers. Consistent with the clin...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1994.tb02046.x
更新日期：1994-08-01 00:00:00
abstract：:An open-label, randomized, crossover study was performed in healthy male volunteers to evaluate the potential pharmacokinetic and pharmacodynamic interactions and tolerability of single oral doses of modafinil (200 mg) and dextroamphetamine (10 mg). Blood samples were collected for determination of plasma levels of mo...
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.tb04395.x
更新日期：1998-10-01 00:00:00
abstract：:Selection of the first dose for neonates in clinical trials is very challenging. The objective of this analysis was to assess if a population pharmacokinetic (PK) model developed with data from infants to adults is predictive of neonatal clearance and to evaluate what age range of prior PK data is needed for informati...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/jcph.524
更新日期：2015-10-01 00:00:00
abstract：:The pharmacokinetic properties of dezocine were examined in 15 patients with acute or chronic pain. In 3 groups of 5 patients each, serum levels were determined at various intervals after single intravenous doses of 5, 10, and 20 mg. After these single doses, dezocine was very rapidly distributed (mean t1/2 alpha less...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1995.tb04080.x
更新日期：1995-04-01 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：:In a placebo-controlled, randomized, double-blind cross-over study in 12 healthy volunteers the effect of acute alcohol intake during treatment with transdermally administered scopolamine (TTS-scopolamine) was investigated. One group of six subjects reached maximal blood alcohol concentrations (BAC) of 80 mg/dL and an...
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.tb05728.x
更新日期：1988-12-01 00:00:00
abstract：:Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin antibiotic. A population pharmacokinetic (PPK) model for ceftaroline was developed in NONMEM® using data from 185 healthy subjects and 92 patients with acute bacterial skin and skin structure infection (ABSSSI). Data from 128 patien...
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.153
更新日期：2013-11-01 00:00:00
abstract：:Food and Drug Administration data show that most anti-depressant studies in youth do not show drug effect. The few positive studies used rigorous diagnostic screening procedures, suggesting major depressive disorder (MDD) may not be a persistent condition in a subgroup of youth. To investigate persistence of MDD, we s...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1177/0091270006290334
更新日期：2006-09-01 00:00:00
abstract：:The pharmacokinetics, pharmacodynamics, and safety of fosinopril sodium (SQ 28,555), a new orally active angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 73 healthy men in two separate studies. In study I, doses ranging from 10 to 640 mg were administered once daily for 3 days to seven groups of five su...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1991.tb01887.x
更新日期：1991-01-01 00:00:00
abstract：:This trial was conducted to evaluate the pharmacokinetics and safety of a sodium oxybate (gamma-hydroxybutyrate [GHB]) oral solution in narcoleptic patients after acute and chronic treatment. An open-label, two-period, two-treatment study design was used. Trial subjects included 13 patients with polysomnographically c...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270003262795
更新日期：2004-03-01 00:00:00
abstract：:Nifedipine kinetics have not been described in clinically relevant detail because of difficulties in formulating a stable preparation for intravenous use and lack of a specific and sensitive assay for plasma nifedipine. We recently developed a gas-chromatographic method and determined conditions in which nifedipine co...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1983.tb02720.x
更新日期：1983-04-01 00:00:00
abstract：:Troglitazone, a PPAR-gamma agonist, enhances the actions of insulin on muscle and liver. It is metabolized predominantly in the liver to a sulfate conjugate and a quinone metabolite. Acetaminophen also undergoes metabolism by conjugation. This three-way crossover study in 12 healthy male volunteers was conducted to in...
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：1998-09-01 00:00:00
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...
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.1552-4604.1986.tb02956.x
更新日期：1986-11-01 00:00:00
abstract：:This was a preliminary feasibility study to assess the pharmacokinetics and acute safety of a single dose of orally inhaled testosterone via the AERx system, a novel handheld aerosol delivery system in postmenopausal women. Twelve postmenopausal women stabilized on oral estrogen therapy were treated with a single dose...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/0091270004269840
更新日期：2005-02-01 00:00:00
abstract：:Traumatic brain injury (TBI) is a major cause of disability and death globally. Despite significant progress in neuromonitoring and neuroprotection, pharmacological interventions have failed to generate favorable results. We examined the effect of memantine on serum levels of neuron-specific enolase (NSE), a marker of...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1002/jcph.980
更新日期：2018-01-01 00:00:00
abstract：:Avibactam is a non-β-lactam β-lactamase inhibitor intended for use as a fixed-dose combination with ceftazidime for the treatment of certain serious Gram-negative infections. As avibactam is primarily excreted unchanged in the urine, renal impairment may affect its pharmacokinetics. This phase 1 study investigated the...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1002/jcph.793
更新日期：2017-02-01 00:00:00
abstract：:This experiment represents the first time that it has been possible to measure a body fluid compartment by direct means during spaceflight. Based on the results observed in the five crewmen in this study, it is concluded that TBW decreases by 3.4% after 1 to 3 days of exposure to microgravity in the Space Shuttle. Som...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1991.tb03663.x
更新日期：1991-10-01 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：:The pharmacokinetics and safety of a single oral dose of 200-mg plant-derived pharmaceutical formulation of highly purified cannabidiol (CBD) in oral solution (Epidiolex in the United States; 100 mg/mL) were assessed in subjects with mild to severe hepatic impairment (n = 8 each for mild and moderate, n = 6 for sever...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1002/jcph.1412
更新日期：2019-08-01 00:00:00
abstract：:The purpose of this study was to characterize the effect of potent CYP2D6 inhibition byparoxetine on atomoxetine disposition in extensive metabolizers. This was a single-blind, two-period, sequential studyin 22 healthy individuals. In period 1, 20 mg atomoxetine bid was administered to steady state. In period 2, 20 mg...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1177/009127002762491307
更新日期：2002-11-01 00:00:00
abstract：:Sixteen healthy male volunteers received a single oral dose of 25 mg doxylamine succinate. Doxylamine concentrations in plasma were measured by a newly developed gas chromatographic methodology, utilizing direct alkaline extraction into hexane:isoamyl alcohol followed by concentration and autoinjection. Doxylamine kin...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1985.tb02875.x
更新日期：1985-09-01 00:00:00
