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 evaluate the effects of co-administration of V on the pharmacokinetics of atenolol (A), and vice versa, and to monitor the pharmacodynamic response of plasma angiotensin II (ANG II) concentrations and plasma renin activity (PRA), as well as of heart rate and blood pressure, under resting and exercise conditions. METHODS:Twelve healthy, normotensive, male volunteers aged 23-46 years were treated with single doses of either 160 mg V or 100 mg A alone, or with both drugs in combination (V + A) according to a three-period crossover design. Plasma concentrations of V and A were determined using HPLC with fluorimetric and UV detection, respectively, and concentration-time profiles were established over 24 h. Plasma ANG II concentrations and PRA were monitored using specific radioimmunoassays. Heart rate and blood pressure were measured at rest and during exercise on a cycle ergometer at a workload of 2.5 W/kg-1. RESULTS:For V, mean AUC and Cmax were slightly higher when A was co-administered, the ratios of log transformed values being 1.13 and 1.22 for AUC(0-inf) and Cmax, respectively. For A, mean AUC and Cmax were slightly lower when the drug was given in combination with V. The ratios of log-transformed values in this case were 0.90 and 0.92, respectively. The sharp increase in plasma ANG II concentrations and PRA, induced by administration of V, was significantly attenuated when the drug was combined with A. In the first 12 h after drug intake, heart rate and systolic blood pressure at rest were significantly decreased when V and A were co-administered compared with treatment with V alone. V given alone did not influence heart rate or systolic blood pressure during exercise, whereas A alone and V + A led to a significant reduction in those variables. Adverse experiences reported after A and V + A could be explained by the high degree of beta-adrenoceptor blockade resulting from the administration of A. CONCLUSIONS:Co-administration of single doses of V and A does not modify the pharmacokinetics of the two drugs to a clinically relevant degree. With respect to pharmacodynamics, a single dose of A attenuates the increase in plasma ANG II and PRA in response to a single dose of V, and V has no effect on the hemodynamic response to exercise. The combined treatment with single doses of 160 mg V and 100 mg A has some additive effects on resting blood pressure in healthy, normotensive subjects.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Czendlik CH,Sioufi A,Preiswerk G,Howald Hdoi
10.1007/s002280050318subject
Has Abstractpub_date
1997-01-01 00:00:00pages
451-9issue
6eissn
0031-6970issn
1432-1041journal_volume
52pub_type
临床试验,杂志文章,随机对照试验abstract::This study assessed the influence of acetylsalicylic acid (ASA, 1.0 g), ibuprofen (0.8 g) and paracetamol (1.0 g) on the single-dose kinetics of ethanol in 12 healthy volunteers ingesting the drug and a standardised 1840-kJ breakfast 1 h before intake of ethanol. It also assessed the influence of ethanol on the single...
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/BF00192741
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abstract:PURPOSE:Intravenous (IV) magnesium sulfate (MgSO4) is used as adjunct therapy to treat acute asthma exacerbations. Despite its clinical use, there is a limited understanding of the disposition of magnesium in children. METHODS:To explore the pharmacokinetics (PK) of IV MgSO4 in this population, we collected retrospect...
journal_title:European journal of clinical pharmacology
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abstract:OBJECTIVE:The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension (OH). METHODS:In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Parkinson's disease, pure autonomic failure, multiple...
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abstract::The influence of a diet deficient in energy or protein on hepatic oxidation (Phase I reactions) and glucuronidation (Phase II reactions) in man has been examined. Nine healthy volunteers were fed an energy deficient diet (daily energy intake 4.3 MJ; daily protein intake 0.94 g/kg) and a protein deficient diet (daily e...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract:PURPOSE:To study the impact of gemfibrozil co-administration on the pharmacokinetics of sitagliptin in healthy Indian male volunteers. METHODS:A randomized open label two-period crossover study involving 12 healthy Indian male volunteers was conducted at a single center. In each phase, the volunteers were administered...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract:PURPOSE:This study compares the in vivo relative lung bioavailability of Hydrofluoroalkane (HFA) Seretide delivered via unprimed and unwashed Aerochamber Plus (AP) or Volumatic (VM) spacers, a integrated breath-actuated vortex Synchro-Breathe (SB) device and an Evohaler pMDI (EH) device using adrenal suppression and ea...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
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abstract::The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharm...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00605631
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abstract::Potentiation of the anticoagulant-effect of warfarin by amiodarone was studied in 30 patients. Thirteen received both drugs concurrently, and 17 received warfarin alone and the combination sequentially. Warfarin doses were adjusted to maintain the prothrombin time between 25-30% of control and its kinetics were compar...
journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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abstract::Accidental intoxication with tramadol of a 6-month old infant was followed by severe cerebral depression. Studies on serum, cerebrospinal fluid, and urine drug levels indicated complete penetration of the blood-cerebrospinal fluid barrier by tramadol. ...
journal_title:European journal of clinical pharmacology
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abstract::The pharmacokinetics of i.v. chloramphenicol succinate and oral chloramphenicol palmitate were studied in Ethiopian children with different nutritional states. In children with kwashiorkor the plasma clearance of chloramphenicol was significantly lower than in children of normal weight (4.16 ml/min/kg versus 7.53 ml/m...
journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
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abstract::The hypocholesterolemic cation resins, cholestyramine and colestipol, have variable effects on the absorption parameters of a number of lipophillic, anion drugs. Because of the unpredictable nature of this interaction, we have assessed in human volunteers the effect of these resins on the rate and total absorption of ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542221
更新日期:1983-01-01 00:00:00
abstract:OBJECTIVE:Case report of a pharmacokinetic interaction between diltiazem and nortriptyline. METHODS:Determination of plasma nortriptyline concentrations by HPLC. Calculation of nortriptyline clearances and half-life by formulae used routinely in therapeutic drug monitoring. RESULTS:The average plasma concentration of...
journal_title:European journal of clinical pharmacology
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更新日期:1996-01-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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abstract:OBJECTIVE:To search for ethnic variability in the impact of cytochrome P450 2C9 (CYP2C9) polymorphism. METHODS:CYP2C9 allelic variants related to impaired CYP2C9 metabolism were analysed in genomic DNA from 157 Spanish healthy subjects using amplification-restriction and sequencing procedures. RESULTS:The frequency f...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2001-04-01 00:00:00
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journal_title:European journal of clinical pharmacology
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更新日期:2000-06-01 00:00:00
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journal_title:European journal of clinical pharmacology
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:2013-03-01 00:00:00
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