Abstract:
PURPOSE:Panobinostat, a potent pan-deacetylase inhibitor, improved progression-free survival (PFS) in patients with relapsed and refractory multiple myeloma when combined with bortezomib and dexamethasone in a phase 3 trial, PANORAMA-1. This study aims to explore exposure-response relationship for panobinostat in this combination in a phase 1 trial, B2207 and contrast with data from historical single-agent studies. METHODS:Panobinostat plasma concentration-time profiles were obtained in patients from PANORAMA-1 (n = 12) and B2207 (n = 12) trials. Overall response rates (ORR) and major adverse events (AE) by panobinostat exposure were investigated in the B2207 trial. Panobinostat PK data from combination trials were contrasted with data from single-agent studies. RESULTS:At maximum tolerated dose (MTD), the geometric mean of panobinostat area under curve from 0 to 24 h (AUC0-24) was 47.5 ng h/mL (77 % CV), and maximum plasma concentration (Cmax) was 8.1 ng/mL (90 % CV). These values were comparable with exposure data obtained in PANORAMA-1, but were 20 % lower than those without dexamethasone, and ∼ 50 % lower from single-agent trials, likely due to enzyme induction by dexamethasone. Higher levels of panobinostat exposure were associated with higher response rates and higher incidences of diarrhea and thrombocytopenia. CONCLUSIONS:Apparent panobinostat exposure-AE and exposure-ORR relationships were observed when combined with bortezomib and dexamethasone in the treatment of patients with relapsed and refractory multiple myeloma. The addition of dexamethasone facilitated best response even though plasma exposure of panobinostat was reduced. Combination with a strong enzyme inducer should be avoided in future trials to prevent further reduction of panobinostat exposure.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Mu S,Kuroda Y,Shibayama H,Hino M,Tajima T,Corrado C,Lin R,Waldron E,Binlich F,Suzuki Kdoi
10.1007/s00228-015-1967-zsubject
Has Abstractpub_date
2016-02-01 00:00:00pages
153-61issue
2eissn
0031-6970issn
1432-1041pii
10.1007/s00228-015-1967-zjournal_volume
72pub_type
杂志文章,随机对照试验abstract:PURPOSE:To develop a limited sampling strategy (LSS) to predict area under the concentration-time curve (AUC) ratios of omeprazole (AUC(OPZ)) to its metabolites 5-hydroxyomeprazole (AUC(5OH)) and omeprazole sulfone (AUC(SUL)) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A. METHODS:Data were obtained f...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-011-1136-y
更新日期:2012-04-01 00:00:00
abstract:OBJECTIVE:Carvedilol, a beta-adrenoceptor blocking agent with additional alpha(1)-adrenoceptor blocking properties, has been shown to improve left ventricular function in chronic heart failure (CHF). However, its effect on mortality has recently been the subject of controversial discussion. The aim of this meta-analysi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s002280050460
更新日期:1998-06-01 00:00:00
abstract::The use of cimetidine in general practice was studied in relation to the guidelines approved by the Dutch National Drug Regulatory Agency (DRA). National and regional figures showed that the frequency with which cimetidine was prescribed in general practice was greater than could be explained on the basis of approved ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542346
更新日期:1983-01-01 00:00:00
abstract:OBJECTIVES:To study the frequency of corticosteroid therapy and the use of inpatient care for preschool children with wheezing in two regions in Finland. METHODS:The Finnish Social Insurance Institution database on refundable asthma medication indicated that 1.18% of children in Tampere and 2.37% in Turku used inhaled...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000199
更新日期:2000-11-01 00:00:00
abstract:OBJECTIVE:We recently reported a highly stereoselective increase in plasma concentrations of (S)-atenolol during exercise which is most likely due to a release of the drug from adrenergic cells. The objective of the present study was to investigate the influence of physical exercise on plasma concentrations of the (R)-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050119
更新日期:1996-01-01 00:00:00
abstract::The kinetics and dynamics of single doses (5 mg p.o.) of the optical isomers of acenocoumarol (R-AC and S-AC) were followed in healthy subjects and the effect on them of cimetidine 800 mg/day was also investigated. The AC enantiomers differed greatly in their pharmacokinetics. The mean residence time (MRT) of R-AC was...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542424
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:The purpose of this study was to ascertain acute liver injury (ALI) in primary care databases using different computer algorithms. The aim of this investigation was to study and compare the incidence of ALI in different primary care databases and using different definitions of ALI. METHODS:The Clinical Practic...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-014-1721-y
更新日期:2014-10-01 00:00:00
abstract:OBJECTIVES:The study was conducted to investigate whether oral co-administration with citrus juices significantly affects the pharmacokinetics and/or pharmacodynamics of pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy male subjects. Grapefruit juice and orange juice, which were both commercially a...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050547
更新日期:1998-11-01 00:00:00
abstract:PURPOSE:Sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes, is reported to be more efficacious in Indian patients than non-Indian patient population. The objective of the study was to evaluate pharmacokinetic and pharmacodynamic (PK/PD) parameters of single-dose sitagli...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-018-2433-5
更新日期:2018-05-01 00:00:00
abstract:PURPOSE:Bosutinib is an oral, dual Src and Abl tyrosine kinase inhibitor (TKI) approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia resistant or intolerant to prior TKI therapy. Bosutinib is primarily metabolized by cytochrome P450 (CYP) 3A4, suggesting drug interaction potential with...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-016-2108-z
更新日期:2017-01-01 00:00:00
abstract::In a cross-over pharmacokinetic study in 8 healthy volunteers a retard formulation containing pindolol 30 mg was compared with the normal 15 mg. pindolol tablet. The pindolol 30 mg retard tablet led to the same maximum plasma level as a single dose of the normal pindolol tablet. A plasma concentration higher than half...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542037
更新日期:1982-01-01 00:00:00
abstract:OBJECTIVE:This study was performed to investigate whether it is possible to use saliva instead of blood usually used for therapeutic drug monitoring (TDM) of disopyramide. METHODS:Six healthy male volunteers ingested 200 mg of disopyramide base, and the disopyramide concentrations in saliva and plasma (total and unbou...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050250
更新日期:1997-01-01 00:00:00
abstract::The effect of indenolol on heart rate and blood pressure at rest and after submaximal workload has been studied in 19 patients with established essential hypertension. A stepwise increase from moderate to submaximal exercise was chosen to mimic challenges normally occurring in daily life. After 4 weeks of once a day i...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00544058
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:Serious adverse effects have been observed with some non-sedative H1-antihistamines (terfenadine and astemizole) when they were associated with drugs known to inhibit their metabolism. However, this is not a class effect, and this interaction should be considered on a case-by-case basis. The aim of this stud...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0917-6
更新日期:2005-06-01 00:00:00
abstract::Methylergometrine, the main metabolite of methysergide, has 40-times greater 5 HT antagonistic potency than methysergide in isolated segments of human temporal artery. It is suggested that methylergometrine is the "active" drug when methysergide is used in migraine prophylaxis, and that the two compounds should be com...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00610384
更新日期:1987-01-01 00:00:00
abstract::The pharmacokinetics of oral L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, and L-threo-DOPS in plasma and urine was determined by high performance liquid chromatogra...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00605999
更新日期:1982-01-01 00:00:00
abstract::A new acid thiol, 2-mercaptopropionate, has been identified by GC-MS in urine from cystinuric patients on treatment with 2-mercaptopropionylglycine. The amount excreted was 50-300 mumol/24h and it was correlated with the oral dose of 2-mercaptopropionyl-glycine. The observation may be of clinical importance as the met...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00871000
更新日期:1986-01-01 00:00:00
abstract::Twenty-four healthy volunteers participated in a study on the disposition of ergotamine following oral and rectal administration. Plasma samples were collected surrounding each dose of medication and a new mass spectrometry method was used for quantitation of the samples. A mean peak plasma concentration of 454 pg/ml ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00541538
更新日期:1986-01-01 00:00:00
abstract::In a multicentre, double-blind, crossover, placebo-controlled study, the antihypertensive effect of labetalol 100 mg and chlorthalidone 10 mg, given alone or in combination, has been assessed in 32 hypertensive patients. The combination had a greater effect in reducing blood pressure than did its separate components. ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00548395
更新日期:1982-01-01 00:00:00
abstract:PURPOSES:Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK o...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-013-1501-0
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:Triptans are contraindicated in patients with known or suspected coronary artery disease (CAD); however, few studies have evaluated triptans in patients with obstructive CAD to quantify the vasoconstrictive effect on diseased coronary vessels. METHODS:Patients undergoing percutaneous transluminal coronary a...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-005-0988-4
更新日期:2005-11-01 00:00:00
abstract::The effect of nevirapine once-daily dosing on the pharmacokinetics of methadone and its main metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, was evaluated in ten HIV positive patients on stable methadone therapy. Nevirapine 200 mg once daily was administered orally from day 1 to day 14. On day 15, nevir...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-007-0299-z
更新日期:2007-07-01 00:00:00
abstract::Anticonvulsants are associated with decreased serum thyroid hormone concentrations. We have studied thyroid function in 54 epileptic patients on a variety of drugs (19 on carbamazepine, 13 on phenytoin, 10 on sodium valproate, 12 on polypharmacy). For comparison, 14 untreated epileptics and 11 healthy unmedicated volu...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558149
更新日期:1989-01-01 00:00:00
abstract::The effects of a beta-blocker, carvedilol, on peripheral hemodynamics and hemorheologic parameters were evaluated in 11 geriatric patients with essential hypertension [3 men and 8 women aged 62-79 years (mean, 68.6 years)]. Carvedilol was given orally after breakfast at a dose of 10 or 20 mg daily for 8 weeks. Periphe...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF01409478
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVE:The aim was to develop a model to describe the population pharmacokinetics of nevirapine in South African human immunodeficiency virus (HIV)-infected patients who were taking nevirapine-based antiretroviral therapy concomitantly or in the absence of rifampicin-based tuberculosis therapy. METHODS:Patients wer...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-008-0481-y
更新日期:2009-01-01 00:00:00
abstract:PURPOSE:A population pharmacokinetic analysis was performed to define domperidone pharmacokinetic parameters in preterm neonates, as no pharmacokinetic data are available in this population. METHODS:An oral domperidone solution was administered (0.75 mg/kg per day) in 32 preterm neonates (64 samples). Domperidone plas...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-008-0535-1
更新日期:2008-12-01 00:00:00
abstract:PURPOSE:The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients. METHODS:A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, ind...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-017-2265-8
更新日期:2017-08-01 00:00:00
abstract:OBJECTIVE:The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. METHODS:Sulfotran...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000168
更新日期:2000-09-01 00:00:00
abstract::The cleansing effects on pus and debris of streptokinase-streptodornase and of stabilized crystalline trypsin were compared in 40 patients (12 males, 28 females) with necrotic varicose or arteriosclerotic leg ulcers. Both preparations produced significant partial or total cleansing of the ulcers of necrotic material, ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00542211
更新日期:1983-01-01 00:00:00
abstract::The effect of procainamide (P) on left ventricular function as measured by the systolic time intervals (STI) was studied in 14 patients with primary myocardial disease. P, 7.5 mg/kg body weight, was given intravenously at a rate of 100 mg per minute. Administration of P produced a decrease in left ventricular performa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561387
更新日期:1980-10-01 00:00:00