当前位置： SCI文献检索 > JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy.

Effect of Vemurafenib on the Pharmacokinetics of a Single Dose of Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Malignancy.

Abstract：

:The primary objective of this phase 1, open-label, multicenter, 3-period, fixed-sequence study was to evaluate the effect of multiple doses of vemurafenib on the pharmacokinetics of a single dose of digoxin, a probe P-glycoprotein (P-gp) substrate, in patients with BRAFV600 mutation-positive metastatic malignancy. Following a 28-day screening period, patients received a single oral dose of digoxin 0.25 mg on day 1 in period A, oral vemurafenib 960 mg twice daily for 21 days in period B (days 8-28), and a single oral dose of digoxin 0.25 mg on day 29 and vemurafenib 960 mg twice a day for 7 days (days 29-35) in period C. Log-transformed area under the concentration-time curve and peak concentration values for digoxin were compared between periods A (digoxin alone) and C (digoxin + vemurafenib) using an analysis of variance model. Twenty-six patients were evaluated for the primary pharmacokinetic analysis. The geometric mean ratio (period C/period A) of area under the curve to the last measurable concentration for digoxin was 1.82 (90%CI 1.63 to 2.02), and the geometric mean ratio of peak concentrations was 1.47 (90%CI 1.30 to 1.65); the 90%CIs were outside of the equivalence limits of 0.82 to 1.22, indicating an effect of vemurafenib on digoxin. Multiple oral doses of vemurafenib were generally well tolerated, with an adverse event profile similar to that previously seen in phase 2 and 3 studies of vemurafenib monotherapy. This study confirmed vemurafenib as an inhibitor of P-gp in vivo with a statistically significant drug-drug interaction with digoxin. Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates.

journal_name

J Clin Pharmacol

journal_title

Journal of clinical pharmacology

authors

Zhang W,McIntyre C,Kuhn M,Forbes H,Kim TM,Lee J,Demidov L,Colburn D

doi

10.1002/jcph.1111

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

1067-1073

issue

8

eissn

0091-2700

issn

1552-4604

journal_volume

58

pub_type

杂志文章

相关文献

JOURNAL OF CLINICAL PHARMACOLOGY文献大全
  • Multiple-dose pharmacokinetics, pharmacodynamics, and safety of taranabant, a novel selective cannabinoid-1 receptor inverse agonist, in healthy male volunteers.

    abstract：:Taranabant is a cannabinoid-1 receptor inverse agonist for the treatment of obesity. This study evaluated the safety, pharmacokinetics, and pharmacodynamics of taranabant (5, 7.5, 10, or 25 mg once daily for 14 days) in 60 healthy male subjects. Taranabant was rapidly absorbed, with a median t(max) of 1.0 to 2.0 hours...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章,随机对照试验

    doi：10.1177/0091270008317591

    authors： Addy C,Rothenberg P,Li S,Majumdar A,Agrawal N,Li H,Zhong L,Yuan J,Maes A,Dunbar S,Cote J,Rosko K,Van Dyck K,De Lepeleire I,de Hoon J,Van Hecken A,Depré M,Knops A,Gottesdiener K,Stoch A,Wagner J

    更新日期：2008-06-01 00:00:00

  • Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low affinity): implications for interactions with enzyme-inducing drugs.

    abstract：:The human cytochrome P450 (CYP) isoforms mediating nortriptyline 10-hydroxylation have been identified using kinetic studies on heterologously expressed human CYPs and chemical inhibition studies on human liver microsomes. Nortriptyline was metabolized to E-10-hydroxynortriptyline by human lymphoblast-expressed CYPs 2...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1177/00912709922008173

    authors： Venkatakrishnan K,von Moltke LL,Greenblatt DJ

    更新日期：1999-06-01 00:00:00

  • Pharmacogenetic Analysis of OATP1B1, UGT1A1, and BCRP Variants in Relation to the Pharmacokinetics of Letermovir in Previously Conducted Clinical Studies.

    abstract：:The cytomegalovirus (CMV) viral terminase inhibitor letermovir is indicated for prevention of CMV infection in CMV-seropositive allogeneic hematopoietic stem cell transplant recipients. In this analysis, functional variants in solute carrier organic anion transporter family member 1B1 (SLCO1B1), uridine diphosphate-gl...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/jcph.1420

    authors： Kobie J,Guo Z,Cho CR,Menzel K,McCrea JB,Blanchard R,Shaw PM

    更新日期：2019-09-01 00:00:00

  • Using student feedback on examination questions to promote fairness, item validity, and learning.

    abstract：:Ten years' experience with a system of modifying the scoring of examinations in pharmacology based on feedback comments from students on individual questions are analyzed. Each examination (3 per year for 10 years), approximately 100 items in length, was subjected to rigorous editing by a faculty committee and an inde...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/j.1552-4604.1997.tb04315.x

    authors： Smith CM

    更新日期：1997-05-01 00:00:00

  • Effect of low-dose omeprazole (20 mg daily) on the pharmacokinetics of multiple-dose atazanavir with ritonavir in healthy subjects.

    abstract：:Atazanavir, a potent protease inhibitor of human immunodeficiency virus (HIV), exhibits pH-dependent solubility. Previous studies have indicated that coadministration with omeprazole 40 mg once daily significantly decreased atazanavir exposure by approximately 75%. Concomitant use of omeprazole and atazanavir is curre...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章,随机对照试验

    doi：10.1177/0091270010367651

    authors： Zhu L,Persson A,Mahnke L,Eley T,Li T,Xu X,Agarwala S,Dragone J,Bertz R

    更新日期：2011-03-01 00:00:00

  • Drug-Drug Interaction Studies With Oral Contraceptives: Pharmacokinetic/Pharmacodynamic and Study Design Considerations.

    abstract：:Oral contraceptives (OCs) are the most widely used form of birth control among women of childbearing potential. Knowledge of potential drug-drug interactions (DDIs) with OCs becomes imperative to provide information on the medication to women of childbearing potential and enable their inclusion in clinical trials, esp...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/jcph.1765

    authors： Sun H,Sivasubramanian R,Vaidya S,Barve A,Jarugula V

    更新日期：2020-12-01 00:00:00

  • Buprenorphine and morphine efficacy in postoperative pain: a double-blind multiple-dose study.

    abstract：:The analgesic activity of buprenorphine was monitored versus that of morphine in a double-blind, randomized, multiple-dose, parallel-design study involving 97 postsurgical patients. Patients could receive intramuscular injections of either buprenorphine (0.3, o.45, or 0.6 mg) or morphine (10, 15, or 20 mg) every 3 or ...

    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.1552-4604.1982.tb02158.x

    authors： Ouellette RD

    更新日期：1982-04-01 00:00:00

  • Lack of interaction between lansoprazole and propranolol, a pharmacokinetic and safety assessment.

    abstract：:Due to the prevalence of both gastrointestinal and cardiovascular diseases, it is likely that patients may be coprescribed gastric parietal cell proton pump inhibitors and beta-adrenergic antagonists. Therefore, the objectives of this phase I study were to assess the potential effects of the coadministration of lansop...

    journal_title：Journal of clinical pharmacology

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1177/00912700022008856

    authors： Karol MD,Locke CS,Cavanaugh JH

    更新日期：2000-03-01 00:00:00

  • Extrapolation of Adult Efficacy to Pediatric Patients With Chemotherapy-Induced Nausea and Vomiting.

    abstract：:Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unneces...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/jcph.1577

    authors： Momper JD,Heinrichs MT,Krudys K,Griebel D,Kumar S,Kim I,Mehrotra N,Mulberg AE,Garimella N,Nelson R,Reaman G,Sinha V,Yao L,Zineh I,Burckart G,Sachs H,Mulugeta Y

    更新日期：2020-06-01 00:00:00

  • Pharmacokinetics of high-dose abetimus sodium in normal subjects with specific assessment of effect on coagulation.

    abstract：:Abetimus sodium is an oligonucleotide-based investigational drug designed to treat patients with lupus nephritis by specifically reducing anti-double-stranded DNA antibody levels. The safety and pharmacokinetics of abetimus were evaluated in 24 healthy volunteers at intravenous doses of 600 mg, 1200 mg, and 2400 mg. T...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章,随机对照试验

    doi：10.1177/0091270008319465

    authors： Linnik MD,O'Rourke AM,Crowther MA

    更新日期：2008-08-01 00:00:00

  • CYP3A5*3 and bilirubin predict midazolam population pharmacokinetics in Asian cancer patients.

    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

    authors： Seng KY,Hee KH,Soon GH,Sapari NS,Soong R,Goh BC,Lee LS

    更新日期：2014-02-01 00:00:00

  • Atorvastatin does not alter the anticoagulant activity of warfarin.

    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

    authors： Stern R,Abel R,Gibson GL,Besserer J

    更新日期：1997-11-01 00:00:00

  • Pharmacokinetics, safety, and tolerability of paliperidone palmitate 3-month formulation in patients with schizophrenia: A phase-1, single-dose, randomized, open-label study.

    abstract：:This multicenter, randomized, open-label, parallel-group, phase-1 study assessed the pharmacokinetics (PK), safety, and tolerability of the investigational intramuscular paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia or schizoaffective disorder. A total of 328 patients (men or women, ...

    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.597

    authors： Ravenstijn P,Remmerie B,Savitz A,Samtani MN,Nuamah I,Chang CT,De Meulder M,Hough D,Gopal S

    更新日期：2016-03-01 00:00:00

  • Are patients reliable when self-reporting medication use? Validation of structured drug interviews and home visits by drug analysis and prescription data in acutely hospitalized patients.

    abstract：:The medication history among hospitalized patients often relies on patients' self-reports due to insufficient communication between health care professionals. The aim of the present study was to estimate the reliability of patients' self-reported medication use. Five hundred patients admitted to an acute medical depar...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1177/0091270007307243

    authors： Glintborg B,Hillestrøm PR,Olsen LH,Dalhoff KP,Poulsen HE

    更新日期：2007-11-01 00:00:00

  • Labetalol in hypertension during the third trimester of pregnancy: its antihypertensive effect and pharmacokinetic-dynamic analysis.

    abstract：:The hypotensive effect, kinetics, and concentration-response relationship of labetalol, alpha beta- and alpha 1-adrenoceptor blocking drug, were studied in seven women with a moderate-to-severe hypertension (averaged diastolic blood pressure [DBP] of 100 to 120 mm Hg measured during a 1- to 2-day hospitalization perio...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/j.1552-4604.1993.tb01933.x

    authors： Saotome T,Minoura S,Terashi K,Sato T,Echizen H,Ishizaki T

    更新日期：1993-10-01 00:00:00

  • Peripheral hemodynamic and humoral effects of oral zofenopril calcium (SQ. 26,991) in patients with congestive heart failure.

    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

    authors： Borghi C,Magelli C,Boschi S,Costa FV,Capelli M,Varani E,Magnani B,Ambrosioni E

    更新日期：1989-12-01 00:00:00

  • Pharmacokinetics, pharmacodynamics, and safety of peginterferon beta-1a in subjects with normal or impaired renal function.

    abstract：:Peginterferon beta-1a was efficacious in a Phase 3 relapsing multiple sclerosis trial, and its safety profile was consistent with other beta interferons. This study evaluated the impact of renal impairment on the pharmacokinetics and pharmacodynamics (neopterin elevation; a biomarker of pharmacological activity induce...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章,多中心研究

    doi：10.1002/jcph.390

    authors： Hu X,Seddighzadeh A,Stecher S,Zhu Y,Goyal J,Matson M,Marbury T,Smith W,Nestorov I,Hung S

    更新日期：2015-02-01 00:00:00

  • Intravitreal Injection of a Rho-Kinase Inhibitor (Fasudil) for Recent-Onset Nonarteritic Anterior Ischemic Optic Neuropathy.

    abstract：:This study evaluated the effects of intravitreal injection of fasudil (IVF), a Rho-kinase inhibitor, in cases of recent-onset nonarteritic anterior ischemic optic neuropathy (NAION). In this interventional case series, 13 eyes of 13 patients diagnosed with NAION within 14 days of onset were included. The affected eyes...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/jcph.655

    authors： Sanjari N,Pakravan M,Nourinia R,Esfandiari H,Hafezi-Moghadam A,Zandi S,Nakao S,Shah-Heidari MH,Jamali A,Yaseri M,Ahmadieh H

    更新日期：2016-06-01 00:00:00

  • Clinical and bacteriological evaluation of amikacin in severe gram-negative infections.

    abstract：:Amikacin was administered to 51 patients with serious Gram-negative infections. A favorable clinical outcome was observed in 32 patients (62 per cent). No major untoward effects were noted. The severity of the underlying disease and the site of the infection were important for the outcome. Urinary tract infections res...

    journal_title：Journal of clinical pharmacology

    pub_type： 临床试验,杂志文章

    doi：10.1002/j.1552-4604.1976.tb01520.x

    authors： Klastersky J,Van Beerse D,Schoutens E,De Temmerman P,Yourassowsky E

    更新日期：1976-04-01 00:00:00

  • A Randomized Controlled Exploratory Pilot Study to Evaluate the Effect of Rotigotine Transdermal Patch on Parkinson's Disease-Associated Chronic Pain.

    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

    authors： Rascol O,Zesiewicz T,Chaudhuri KR,Asgharnejad M,Surmann E,Dohin E,Nilius S,Bauer L

    更新日期：2016-07-01 00:00:00

  • Characterization of Neutropenia in Advanced Cancer Patients Following Palbociclib Treatment Using a Population Pharmacokinetic-Pharmacodynamic Modeling and Simulation Approach.

    abstract：:Neutropenia is the most commonly reported hematologic toxicity following treatment with palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for metastatic breast cancer. Using data from 185 advanced cancer patients receiving palbociclib in 3 clinical trials, a pharmacokinetic-pharmacodynamic model was develo...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章,随机对照试验

    doi：10.1002/jcph.902

    authors： Sun W,O'Dwyer PJ,Finn RS,Ruiz-Garcia A,Shapiro GI,Schwartz GK,DeMichele A,Wang D

    更新日期：2017-09-01 00:00:00

  • Pharmacokinetics of didanosine and ketoconazole after coadministration to patients seropositive for the human immunodeficiency virus.

    abstract：:The steady-state pharmacokinetics of didanosine (DDI) and ketoconazole (KET) were evaluated when the agents were administered alone or concurrently to patients seropositive for the human immunodeficiency virus. Using a randomized, three-way crossover design, multiple oral doses of DDI (375 mg twice daily for 4 days), ...

    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.1552-4604.1993.tb01921.x

    authors： Knupp CA,Brater DC,Relue J,Barbhaiya RH

    更新日期：1993-10-01 00:00:00

  • Dosing regimen of gentamicin during intermittent peritoneal dialysis.

    abstract：:The peritoneal clearance of gentamicin was studied in 11 chronic uremic patients who undergoing intermittent peritoneal dialysis. Gentamicin was significantly removed by peritoneal dialysis with a clearance value of 9.75 +/- 3.78 ml/min. The serum half life was 14.08 +/- 3.57 hr, a value significantly less than that o...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/j.1552-4604.1989.tb03302.x

    authors： Kaojarern S,Arkaravichien W,Indraprasit S,Pummangura C

    更新日期：1989-02-01 00:00:00

  • A comparison of the anti-hypertensive effectiveness of two triameterene/hydrochlorothiazide combinations: Maxzide versus Dyazide.

    abstract：:The hydrochlorothiazide component of Maxzide (Lederle Laboratories, Pearl River, NY) has been shown to be more bioavailable than the hydrochlorothiazide component of Dyazide (Smith, Kline and French Laboratories, Philadelphia, PA). The authors compared the antihypertensive effectiveness of a half-tablet of Maxzide (25...

    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.1552-4604.1990.tb03632.x

    authors： Casner PR,Dillon KR

    更新日期：1990-08-01 00:00:00

  • Single- and multiple-dose pharmacokinetics of intravenous cefpirome (HR810) to healthy volunteers.

    abstract：:The safety and pharmacokinetics of single and multiple administrations of cefpirome (HR810), a new cephalosporin antibiotic agent with a broad antibacterial spectrum, were studied in healthy male volunteers. The single administration protocols included a 3-minute intravenous injection of 0.5 g or 1 g, and a 1-hour int...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章,评审

    doi：10.1002/j.1552-4604.1992.tb03834.x

    authors： Nakayama I,Akieda Y,Yamaji E,Nitta Y,Ohishi M,Katagiri K,Imamura N,Takase K

    更新日期：1992-03-01 00:00:00

  • Influence of food on the bioavailability of trimoprostil: an overview.

    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

    authors： Wills RJ

    更新日期：1984-04-01 00:00:00

  • Use of reflectance spectrophotometry in the human corticosteroid skin blanching assay.

    abstract：:A reflectance spectrophotometric method for evaluation of the skin blanching response to topical corticosteroids was evaluated. This blanching response is used, for drug development and regulatory purposes, to assess potency and bioequivalence of topical corticosteroid products. The common method involves the use of a...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/j.1552-4604.1993.tb05611.x

    authors： Conner DP,Zamani K,Almirez RG,Millora E,Nix D,Shah VP

    更新日期：1993-08-01 00:00:00

  • Ovulation-inhibiting effects of dienogest in a randomized, dose-controlled pharmacodynamic trial of healthy women.

    abstract：:Dienogest offers pharmacological advantages for the effective treatment of endometriosis and for use in contraception and hormone replacement therapy. This pharmacodynamic study investigated the ovulation-inhibiting effects of dienogest monotherapy in healthy women. Dienogest was administered at 0.5, 1, 2, or 3 mg dai...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章,随机对照试验

    doi：10.1177/0091270011423664

    authors： Klipping C,Duijkers I,Remmers A,Faustmann T,Zurth C,Klein S,Schuett B

    更新日期：2012-11-01 00:00:00

  • Lack of effect of enoximone on the pharmacokinetics of digoxin in patients with congestive heart failure.

    abstract：:The aim of this study was to investigate if the concomitant administration of the positive inotropic drug enoximone (100 mg tid) has any effect on the morning through levels of the cardiac glycoside digoxin in 17 patients with congestive heart failure (NYHA II-IV). Plasma concentrations of digoxin were 1.05 +/- 0.37 n...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/j.1552-4604.1990.tb03467.x

    authors： Trenk D,Hertrich F,Winkelmann B,Glauner T,Dieterich HA,Jähnchen E

    更新日期：1990-03-01 00:00:00

  • Interrelationships among thiazide diuretics and calcium, magnesium, sodium, and potassium balance in normal and hypertensive man.

    abstract：:The benzothiadiazide diuretics are known to cause magnesium and potassium wasting and retention of calcium and uric acid. The effect of magnesium replacement on diuretic-induced changes in sodium, potassium, calcium, and magnesium balance, weight, and blood pressure was studied in 12 normal subjects and 13 hypertensiv...

    journal_title：Journal of clinical pharmacology

    pub_type： 杂志文章

    doi：10.1002/j.1552-4604.1978.tb01582.x

    authors： Sullivan JM,Dluhy RG,Wacker WE,Solomon HS,Williams GH,Samaha JK

    更新日期：1978-11-01 00:00:00