Abstract:
PURPOSE:The effect of posaconazole, a strong cytochrome P450 3A (CYP3A) inhibitor and commonly used antifungal agent, on the pharmacokinetic properties of venetoclax, a CYP3A substrate, was evaluated in patients with acute myeloid leukemia to determine the dose adjustments needed to manage this potential interaction. METHODS:Twelve patients received 20- to 200-mg ramp-up treatment with oral venetoclax and 20 mg/m2 of intravenous decitabine on days 1 through 5, followed by 400 mg of venetoclax alone on days 6 through 20. On days 21 through 28, patients received 300 mg of posaconazole plus reduced doses of venetoclax (50 or 100 mg) to account for expected increases in venetoclax plasma concentrations. Blood samples were collected before dosing and up to 24 hours after the venetoclax dose on days 20 and 28. FINDINGS:Compared with a venetoclax dose of 400 mg when administered alone (day 20), coadministration of venetoclax at a 50-mg dose with multiple doses of posaconazole increased mean venetoclax Cmax and AUC0-24 by 53% and 76%, respectively, whereas coadministration of venetoclax at a 100-mg dose with posaconazole increased mean venetoclax Cmax and AUC0-24 by 93% and 155%, respectively. When adjusted for different doses and nonlinearity, posaconazole was estimated to increase venetoclax Cmax and AUC0-24 by 7.1- and 8.8-fold, respectively. Both the 50- and 100-mg venetoclax doses administered with posaconazole were well tolerated. IMPLICATIONS:The results are consistent with inhibition of CYP3A-mediated metabolism of venetoclax. Posaconazole can be used for antifungal prophylaxis in patients with acute myeloid leukemia receiving venetoclax after reducing the venetoclax dose by at least 75%. ClinicalTrials.gov identifier: NCT02203773.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Agarwal SK,DiNardo CD,Potluri J,Dunbar M,Kantarjian HM,Humerickhouse RA,Wong SL,Menon RM,Konopleva MY,Salem AHdoi
10.1016/j.clinthera.2017.01.003subject
Has Abstractpub_date
2017-02-01 00:00:00pages
359-367issue
2eissn
0149-2918issn
1879-114Xpii
S0149-2918(17)30036-Xjournal_volume
39pub_type
杂志文章abstract:BACKGROUND:Enzyme replacement therapy (ERT) with imiglucerase is a well-established, effective treatment for Gaucher disease. However, there have been no published reports regarding the excretion of imiglucerase into human breast milk and its effects on the nursing infant. OBJECTIVE:This letter reports on the successf...
journal_title:Clinical therapeutics
pub_type: 信件
doi:10.1016/j.clinthera.2010.11.008
更新日期:2010-11-01 00:00:00
abstract::Immediate complications of trauma and shock include right heart failure, acute respiratory distress syndrome, coagulopathy, brain edema, small bowel dysfunction, renal failure, and immune dysfunction. Nosocomial infections are also common in trauma patients. These infections are the combined result of a compromised ho...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1990-01-01 00:00:00
abstract:PURPOSE:Public discourse regarding the hepatitis C virus (HCV) drug Sovaldi® (sofosbuvir) has become inflamed, generating much heat but little light concerning the clinical, health economic, and quality-of-life merits of Sovaldi®. The purpose of this article is to provide a factual basis for evaluating the claims regar...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2015.02.009
更新日期:2015-05-01 00:00:00
abstract:PURPOSE:Levodopa (LD) is the most effective oral pharmacotherapy for the management of motor symptoms in Parkinson's disease. However, LD use is complicated by a progressive shortening of the duration of efficacy of a dose, resulting in episodes of inadequate responsiveness, or OFF periods. OFF periods may also occur u...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.04.004
更新日期:2020-06-01 00:00:00
abstract:BACKGROUND:The use of dry-powder inhalers (DPIs) to administer respiratory medicines is increasing, and new DPIs are likely to be developed because of expiring patents. However, there is considerable debate concerning the extent to which DPIs are interchangeable without altering disease control or the safety profile of...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2009.02.007
更新日期:2009-02-01 00:00:00
abstract::Lidocaine generally is the agent of first choice against acute ventricular arrhythmias arising from many causes. It is clinically effective and well tolerated, having a rapid onset of action and a favorable electrophysiological profile. Unlike other antiarrhythmic agents, lidocaine does not interact with the autonomic...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:Patients newly diagnosed with type 2 diabetes mellitus generally initiate therapy with either metformin [Met] or a sulfonylurea [SU] drug, followed by the addition of a second agent (Met, an SU drug, or a thiazolidinedione [TZD] drug) if the diabetes is not well controlled. If necessary, the usual third line...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.10.018
更新日期:2011-12-01 00:00:00
abstract::The medical records for 174 patients who underwent cholecystectomy (n = 52) or hip/knee replacement (n = 122) at four community-based medical centers were retrospectively reviewed to determine if using a nonnarcotic alternative to morphine sulfate and/or meperidine as a primary postoperative analgesic could reduce res...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究
doi:
更新日期:1993-09-01 00:00:00
abstract::This study compared the cost-effectiveness of donepezil, a new cholinesterase inhibitor indicated for the treatment of mild-to-moderate probable Alzheimer's disease (AD), with no treatment. A Markov state transition model was employed to simulate treatment costs based on Swedish epidemiologic data. The Markov states u...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)80025-9
更新日期:1999-07-01 00:00:00
abstract:BACKGROUND:Technologies in which a remote trigger is used to release drug from an implanted or injected device could enable on-demand release profiles that enhance therapeutic effectiveness or reduce systemic toxicity. A number of new materials have been developed that exhibit sensitivity to light, ultrasound, or elect...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2012.09.012
更新日期:2012-11-01 00:00:00
abstract:PURPOSE:Long-acting insulin analogues were developed to facilitate consistent glycemic control without excessive hypoglycemia. However, structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors. The aim of this study was to estimate the risk of s...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.06.031
更新日期:2014-09-01 00:00:00
abstract:BACKGROUND:Poor glycemic control in hospitalized patients has been associated with increased morbidity and mortality. Research suggests that analogue bolus insulin may be more effective in achieving blood glucose (BG) control compared with human bolus insulin. OBJECTIVE:This study compares mortality, length of stay (L...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.10.009
更新日期:2010-10-01 00:00:00
abstract::The purpose of this clinical study was to determine the efficacy, tolerability, and impact on quality of life of domperidone--a specific peripherally acting dopamine antagonist--in the management of symptoms of gastroparesis, a common and potentially debilitating condition in patients with diabetes mellitus. In the fi...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(98)80054-4
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND:Granisetron, a selective 5-hydroxytryptamine3 antagonist, is effective for the treatment of patients with postoperative nausea and vomiting. Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. OBJECTIVE:This study compared the efficacy of granisetron alone with granisetr...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验,收录出版
doi:10.1016/s0149-2918(03)80092-9
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND:The off-label use of beta-blockers might be prevalent, but no studies have provided empiric data on the off-label use based on utilization data. OBJECTIVE:This secondary data analysis was conducted to describe the trends of off-label use of beta-blockers among ambulatory visits made to office-based physicia...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2006.10.015
更新日期:2006-10-01 00:00:00
abstract::Nonadherence to recommended pneumococcal conjugate vaccine (PCV) schedules may have implications for protection against pneumococcal disease. In this commentary, we have assessed adherence to the recommended dosing schedules (the completion of the primary PCV and booster series) in different European countries. We fou...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.03.001
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:Combination therapy with at least 2 antihypertensive agents is usually needed to achieve appropriate blood pressure (BP) control in patients with isolated or predominant systolic hypertension. A currently recommended combination is a diuretic added to an angiotensin-receptor blocker. OBJECTIVE:This was a st...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2005.07.010
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND:Besifloxacin is a topical fluoroquinolone with potent in vitro activity against a broad spectrum of ocular pathogens, including drug-resistant strains. Besifloxacin ophthalmic suspension 0.6% given 3 times daily for 5 days has been reported to be more effective than its vehicle in the treatment of bacterial ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2010.12.004
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Patients with hypertension may require combination therapy to attain the blood pressure targets recommended by US and European treatment guidelines. Combination therapy with a calcium channel blocker and an angiotensin II-receptor blocker would be expected to provide enhanced efficacy. OBJECTIVES:Two studie...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2007.03.018
更新日期:2007-04-01 00:00:00
abstract::A phase II study of weekly low-dose doxorubicin (6 to 12 mg/m2) showed it to be an effective, well-tolerated therapy in advanced breast cancer. Although most of the 34 patients studied had been clinically resistant to previous endocrine measures and/or other kinds of chemotherapy, had a median score of 60 on Karnofsky...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::Six hundred forty-eight patients (50.5% men; 49.5% women) with diabetes mellitus on animal-source insulin therapy for at least five years were studied. In this patient population, approximately 68.7% had Type I insulin-dependent diabetes mellitus and 31.3% had Type II noninsulin-dependent diabetes mellitus, nonetheles...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1991-09-01 00:00:00
abstract:BACKGROUND:Hereditary angioedema (HAE) is a rare, potentially life-threatening autosomal dominant disease characterized by recurrent angioedema attacks that affect the skin, gastrointestinal tract, and airway, including the larynx. Pharmacologic developments in HAE treatment have culminated in the recent introduction o...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.02.003
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND:Partial seizure disorder is typically treated by monotherapy with antiepileptic drugs (AEDs). However, when the condition is refractory to the initial treatment regimen, patients may be switched to monotherapy with another AED or to combination therapy with the initial AED plus a second AED. OBJECTIVES:The ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.10.020
更新日期:2005-10-01 00:00:00
abstract:INTRODUCTION:Acute generalized exanthematous pustulosis (AGEP) is a clinical reaction pattern that is principally drug induced and is characterized by acute, extensive formation of nonfollicular sterile pustules on an erythematous and edematous substrate. Hydroxychloroquine (HHCQ), an antimalarial drug widely used to t...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2008.05.014
更新日期:2008-05-01 00:00:00
abstract::Allylestrenol was used to treat 375 women with threatened pregnancies. Results show that this drug is capable of maintaining pregnancy in a large series of ambulant patients and is safe for both mother and child. Allylestrenol does not maintain pregnancy if placental dysfunction is present, however. Newborns whose mot...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract::A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with treatment regimens including the angiotensin II receptor antagonist losartan, with hydrochlorothiazide (HCTZ) added as needed, with regimens includ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(96)80212-8
更新日期:1996-07-01 00:00:00
abstract:BACKGROUND:Cytochrome P450-related drug interactions can lead to adverse effects that may affect health care resource utilization. OBJECTIVE:The purpose of this study was to quantify the impact of drug interactions involving hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) on health care resource utiliz...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(02)80102-3
更新日期:2002-12-01 00:00:00
abstract::Serum creatinine and beta 2-microglobulin levels, endogenous creatinine clearance, the urinary beta 2-microglobulin excretion rate, and urinary protein levels were monitored serially in 29 patients with duodenal ulcers randomly allocated to receive eight weeks of treatment with cimetidine, ranitidine, or an antacid. A...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:Tapentadol hydrochloride is a centrally acting oral analgesic approved by the US Food and Drug Administration in November 2008 for the treatment of moderate to severe acute pain. It is available as immediate-release 50-, 75-, and 100-mg tablets. OBJECTIVE:The purpose of this article is to review animal stud...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2009.12.003
更新日期:2009-12-01 00:00:00
abstract::The monomeric insulin analogue insulin lispro (Lys B28, Pro B29) is a rapid-acting insulin with a shorter duration of activity than human regular insulin. This compound has the advantage of reducing early postprandial hyperglycemia and the accompanying late hypoglycemia, thereby improving overall blood glucose control...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(98)80040-4
更新日期:1998-01-01 00:00:00