Abstract:
PURPOSE:LCZ696 (sacubitril/valsartan), an angiotensin receptor neprilysin inhibitor, is indicated for chronic heart failure (HF) and reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and hospitalization for HF. Following oral administration, LCZ696 provides systemic exposure to valsartan and sacubitril (a prodrug), and its metabolite sacubitrilat (the active neprilysin inhibitor, formerly named as LBQ657), which is eliminated primarily via renal route. Since renal dysfunction is a common comorbidity in patients with HF, two open-label studies assessing the effect of mild, moderate, and severe renal impairment were conducted. METHODS:Patients with mild (N = 8; creatinine clearance [CrCl] 50 to ≤80 mL/min), moderate (N = 8; CrCl 30 to <50 mL/min), and severe (N = 6; CrCl <30 mL/min) renal impairment and matching healthy subjects (CrCl >80 mL/min) for each severity group were enrolled to assess the pharmacokinetics of LCZ696 analytes following administration of LCZ696 400 mg once daily (QD) on days 1 and 5. RESULTS:The steady-state Cmax and AUC0-24h of sacubitril and valsartan were unchanged in patients with renal impairment compared with healthy subjects. However, the steady-state Cmax of sacubitrilat was increased by ∼60 % in patients irrespective of degree of renal impairment; half-life increased from 12 h (in healthy subjects) to 21.1, 23.7, and 38.5 h, respectively; and AUC0-24h was increased 2.10-, 2.24-, and 2.70-fold, respectively, in patients with mild, moderate, and severe renal impairment. CONCLUSION:Renal dysfunction increases exposure to sacubitrilat while not impacting sacubitril and valsartan exposure. LCZ696 was generally well tolerated in patients with renal impairment.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Ayalasomayajula SP,Langenickel TH,Jordaan P,Zhou W,Chandra P,Albrecht D,Pal P,Rajman I,Sunkara Gdoi
10.1007/s00228-016-2072-7subject
Has Abstractpub_date
2016-09-01 00:00:00pages
1065-73issue
9eissn
0031-6970issn
1432-1041pii
10.1007/s00228-016-2072-7journal_volume
72pub_type
杂志文章abstract::The pharmacokinetics of isosorbide-5-mononitrate (IS-5-MN) has been studied in two groups of healthy volunteers after oral (n = 20) and intravenous (n = 11) administration of 20 mg, which had previously been proved to be as effective as 20 mg sustained-release isosorbide dinitrate (ISDN). IS-5-MN in serum was measured...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00618777
更新日期:1981-01-01 00:00:00
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::Nine healthy adults were administered indocyanine green (ICG) 0.5 mg.kg-1 IV alone and after the administration of the following oral drugs: nifedipine 10 mg, propranolol 80 mg, propranolol 80 mg and nifedipine 10 mg, and propranolol 80 mg after nifedipine 10 mg every 8 h for 5 days. Heart rate and mean arterial blood...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00679780
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:Valsartan (V), a specific inhibitor of the angiotensin II receptor subtype, AT1, has been developed for treatment of hypertension. Combination therapy with a beta-adrenoceptor blocking agent might be considered in cases with insufficient efficacy of V alone. Therefore, an interaction trial was performed to ev...
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/s002280050318
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:In this review, we focus on the clinical and radiological aspects related to the biological therapy of ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). METHODS:A review was carried out in the main medical databases to evaluate the available literature. RESULTS:Even if ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-014-1706-x
更新日期:2014-09-01 00:00:00
abstract:PURPOSE:To assess, with all available trial information, whether the assessment of the PRECIS-2 nine domains could provide a clear distinction between medicine masked pragmatic randomized controlled trials (pRCTs) and open-label pRCTs. METHODS:A search was conducted of participant-level pRCTs on medicines published on...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-03030-8
更新日期:2020-10-26 00:00:00
abstract::The pharmacokinetics of mexiletine, a Class I antiarrhythmic drug, was investigated in 6 healthy volunteers after single oral doses and 15 min intravenous infusions of 3 mg/kg. Cimetidine and ranitidine are commonly used H2-receptor antagonists, which interact adversely with many drugs, e.g. inhibition of the metaboli...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558298
更新日期:1989-01-01 00:00:00
abstract::The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I). The pharmacokinetic parameters of the act...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF02284968
更新日期:1992-01-01 00:00:00
abstract::The acute effects on monophasic action potentials (MAP), QT interval, and right ventricle effective refractory period (V-ERP) of propranolol 0.2 mg.kg-1 body weight have been studied in 10 patients with coronary artery disease. The median duration of MAP at 90% repolarization (MAP90) was shortened from 238 to 228 ms a...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00280044
更新日期:1990-01-01 00:00:00
abstract::In a double blind, randomised trial, the effects of 1 g aspirin and 1 g paracetamol were compared on bleeding time and platelet aggregation in 40 volunteers (20 females). Also investigated was the relationship between plasma aspirin esterase activity and both bleeding time and platelet aggregation after aspirin. Follo...
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/BF00543486
更新日期:1984-01-01 00:00:00
abstract::Protein binding of phenytoin was assesed in one patient with dialysis encephalopathy before and after haemodialysis. Phenytoin concentrations were measured by radioimmunoassay and continuous ultrafiltration was used to assess phenytoin binding. At a serum concentration of 60 micromol.1-1 the percentage of phenytoin bo...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00563560
更新日期:1979-02-19 00:00:00
abstract::Hemodynamic changes for 30 min after intravenous administration of molsidomin 4 mg were studied in 10 patients. Pulmonary artery pressure, pulmonary wedge pressure, right atrial pressure and aortic pressure decreased significantly after 15 min, and after 30 min they were still below the control level. Heart rate incre...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00716357
更新日期:1978-06-19 00:00:00
abstract::Caffeine metabolites in urine from premature infants were analysed by TLC and HPLC. Caffeine, dimethyluric acids, mono- and dimethylxanthines and, for the first time, a uracil derivative (6-amino-5-[N-methylformylamino]-1,3-dimethyluracil) were identified. ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00613531
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVES:Evidence exists to suggest that diclofenac is metabolised by CYP2C9. The present study was undertaken in order to evaluate the effect of the single CYP2C9*3 variant on drug metabolism using diclofenac as a probe drug. METHODS:A single dose of diclofenac was administered orally to 12 healthy subjects in whom...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050722
更新日期:2000-04-01 00:00:00
abstract::The gastric inhibitory effects of CM57755, a new histamine H2 receptor antagonist, have been compared in ten healthy male volunteers with the actions of an equal dose of cimetidine and with placebo. The inhibitory effect of CM57755 was virtually identical with, and not significantly different from the effects of cimet...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00614192
更新日期:1986-01-01 00:00:00
abstract::Plasma levels of canrenone and 'total metabolites' after base hydrolysis were compared in young and elderly subjects following single and multiple doses of spironolactone. After the initial dose on Day 1, plasma levels of canrenone and 'total metabolites' were higher in the young than in the elderly group, and signifi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00549591
更新日期:1984-01-01 00:00:00
abstract::The effects of the ingestion of food and digoxin on the cardiovascular system alone and in combination have been observed in eight healthy subjects. A positive inotropic response was seen following food (2.5 MJ) and intravenous digoxin (0.01 mg/kg) with significant decreases in QS2Index (QS2I) pre-ejection period (PEP...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00615959
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:To investigate the characteristics of ADRs in patients admitting at the emergency room of a tertiary hospital. METHODS:We collected the patient records of 1600 emergency room visits of a university hospital in 2018. The patient files were studied retrospectively and all possible ADRs were identified and regist...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-03043-3
更新日期:2020-11-13 00:00:00
abstract:INTRODUCTION:Deoxycytidine kinase (DCK) is the rate-limiting enzyme of the intracellular phosphorylation of nucleoside anticancer drugs, including gemcitabine and beta-arabinofuranosylcytosine, to their active triphosphates. This study was performed to assess the occurrence and frequency of DCK polymorphisms in a predo...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-006-0162-7
更新日期:2006-08-01 00:00:00
abstract::The relationship between the pharmacokinetics and pharmacodynamics of enoximone, a new positive inotropic agent, was investigated in 6 healthy men. The volunteers received single oral and i.v. doses of 3 and 1 mg/kg, respectively, and placebo in a double-blind cross-over trial. Plasma concentrations of enoximone and i...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00637599
更新日期:1988-01-01 00:00:00
abstract::The pharmacokinetics of intravenous chloramphenicol has been studied in 42 patients with liver disease and in 8 controls. The half-life of chloramphenicol (t 1/2) was increased in the various liver disorders, the metabolic clearance rate (MCR) and apparent volume of distribution (Vd) were decreased and the area under ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542103
更新日期:1981-01-01 00:00:00
abstract::The effects of the beta-blocker atenolol on vigilance, concentration, and psychophysiological condition were determined by measuring visual reaction time and choice reaction time in volunteers subjected to combined physical and mental stress. Atenolol 50 mg or placebo were administered for three days in a double-blind...
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/BF00543710
更新日期:1985-01-01 00:00:00
abstract::The effects of acute and chronic administration of a slow-release preparation of pinacidil have been studied in eight normotensive volunteers aged 40-57 years. Continuous administration of 20 mg b.i.d. pinacidil had no effect on serum pinacidil concentrations measured as AUC (0-9 h), but accumulation of the principal ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00555515
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVE:In order to document the stereoselective distribution in joints of a chiral nonsteroidal anti-inflammatory drug, the relative affinities of the enantiomers of tiaprofenic acid in synovium and for cartilage were compared. METHODS:The distribution of tiaprofenic acid in synovium and in cartilage was studied 25...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050109
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to add to the body of evidence on statin-induced gynecomastia based on data retrieved from the Italian spontaneous adverse drug reaction (ADR) reporting database. METHODS:Spontaneous ADR reports collected in the Italian database up to 31 December 2010 were assessed on a case-by-case b...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-012-1218-5
更新日期:2012-06-01 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::The pharmacodynamic actions and disposition of diuretic and antihypertensive agents may be significantly modified in subjects with renal disease. Most studies on this question have dealt with alterations in the elimination kinetics of these drugs and, while they generate descriptive data, minimal insight about change...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561487
更新日期:1980-07-01 00:00:00
abstract::We have evaluated the effects of repaglinide, a new non-sulphonylurea oral hypoglycaemic agent that has a stimulatory effect on insulin secretion. Forty-four patients with NIDDM, already treated with a sulphonylurea, took part in an open, randomised, group comparison study of 12 weeks duration, during which they recei...
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/BF00315490
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:Ticagrelor is a reversibly binding P2Y12 receptor antagonist for the prevention of atherothrombotic events in patients with acute coronary syndrome. Previous in vitro studies showed that ticagrelor is a substrate and inhibitor of P-glycoprotein (ABCB1). Therefore, we examined the potential interaction between d...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-013-1543-3
更新日期:2013-10-01 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