依那普利治疗原发性高血压病80例的疗效观察

选择用依那普利治疗原发性高血压病人80例,与用卡托普利治疗的病人80例进行疗效比较.结果表明前者的降压有效率较高(86.25%).用依那普利的治疗组血压平均下降17.5%,卡托普利对照组为12.7%.使用依那普利没有发现明显的不良反应,它的血浆半衰期长,具有持续的降压作用.     

Systemic Availability of Acetylsalicylic Acid in Human Subjects after Oral Ingestion of Three Different Formulations

Abstract: Systemic availability of acetylsalicylic acid (ASA) in normal human subjects after oral ingestion of 1 g in three different formulations was determined by using high-pressure liquid chromatography for ASA assay. For an effervescent, a plain and a sustained release preparation systemic availabilities expressed in percent of the ingested dose were 16.9±3.2, 8.6±1.2 and 2.6±0.4%, respectively. All subjects had clearly measureable amounts of ASA in plasma after oral intake of a sustained release preparation with an average peak concentration of 15 μmol/1. Peak concentration after an effervescent and plain formulation was on the average 80 and 40 μmol/1, respectively. Half-life of ASA in plasma was 18.1±1.2 min. for the effervescent and 28.7±5.3 min. for the plain preparation, while the elimination phase was too ill defined for the sustained release formulation. Average plasma half-life of salicylic acid (SA) was similar after the three different administration forms with values between 3.0 and 3.7 hrs. Further, no difference in SA distribution volumes or amounts of SA absorbed was found. The present study demonstrates that oral ingestion of ASA in effervescent, plain and sustained release formulations gives rise to significant amounts of ASA in plasma. Concentrations found indicate that long-term antithrombotic therapy with ASA in a sustained release formulation may be possible.     

Selective and validated spectrophotometric methods for the determination of nicorandil in pharmaceutical formulations

Two simple and sensitive validated spectrophotometric methods have been described for the assay of nicorandil in drug formulations. Method A is based on the reaction of the drug with phloroglucinol-sulfanilic acid reagent in sulfuric acid medium to give yellow-colored product, which absorbs maximally at 425 nm. Method B uses the oxidative coupling of 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) with DL- 3,4 - dihydroxyphenylalanine (DL-dopa) in the presence of nicorandil as oxidant in sulfuric acid medium to form an intensely colored product having maximum absorbance at 530 nm. Beer's law is obeyed in the concentration range 2.5 to 50.0 and 1.0 to 15.0 microg mL(-1) with methods A and B, respectively. Both methods have been successfully applied for the analysis of drug in pharmaceutical formulations. The reliability and the performance of the proposed methods are established by point and interval hypothesis and through recovery studies. The experimental true bias of all samples is smaller than +/-2%.     

A Dynamic Artificial Gastrointestinal System for Studying the Behavior of Orally Administered Drug Dosage Forms Under Various Physiological Conditions

PURPOSE: The purpose of this study was to demonstrate the potential of a dynamic, multicompartmental in vitro system simulating the human stomach and small intestine (TIM-1) for studying the behavior of oral drug dosage forms under various physiological gastrointestinal conditions. METHODS: Two model drug compounds were studied in TIM-1: a lyophilized Lactobacillus strain and paracetamol (acetaminophen). The Lactobacillus survival rate was determined by bacterial counting in the gastric and ileal effluents while simulating the conditions of the gastrointestinal tract of infants or adults. The availability for absorption of paracetamol from two oral dosage forms was investigated by measuring the drug concentration in jejunal dialysis fluid. The effect of gastrointestinal passage time and food intake on paracetamol absorption was also studied. RESULTS: The Lactobacillus survival rate in both gastric and ileal effluents was higher during simulation of the infant compared to adult conditions. We also showed that (i) paracetamol absorption was faster when it was administered as a free powder than in sustained-release tablet form, (ii) a slow passage time resulted in a delay in the absorption of paracetamol, and (iii) there was a lower rate of absorption when paracetamol was ingested with a standard breakfast as opposed to water. The in vitro results were consistent with in vivo data, showing the predictive value of TIM-1. CONCLUSIONS: TIM-1 is a powerful tool for supplying valuable information about the effects of various gastrointestinal conditions on biopharmaceutical behavior and efficacy of drug delivery systems in the development of oral formulations.     

Pharmacokinetics of an ultralong sustained-release theophylline formulation when given twice daily in elderly patients with chronic obstructive pulmonary disease: monitoring implications

The steady-state pharmacokinetics of an ultralong sustained release formulation of theophylline (Unilong) twice daily (bid) in elderly hospitalized patients suffering from chronic obstructive pulmonary disease (COPD) have been studied in order to establish guidelines for monitoring. The study was carried out in 37 patients (33 men), aged 60-87 years. Samples were collected from 0 to 12 h after the morning dose on day 9 of treatment with 250 mg bid (n=25) or 375 mg bid (n=12). Considerable variability in apparent clearance (range 0.33-1.49 ml/min per kg of ideal body weight), Css(min)/D (range 0.28-1.86), Css(max)/D (range 0.65-2.33) and (Css(max)-Css(min))/Css(avg) (range 0.18-0.80) was observed. There was no significant correlation between the patient's age and apparent clearance within this elderly population. The concentration-to-dose ratio and the relationship between the steady-state plasma concentration at different times during the dosage interval and Css(avg) are described. It is concluded that the interpatient variability in peak-trough fluctuation of this formulation was higher than that described in healthy volunteers by other investigators, and that the apparent clearance did not decrease with age within this elderly population with COPD. The importance of theophylline monitoring is emphasized and rules to estimate Css(avg) and Css(5h) from Css(0h) when only a single sample obtained before the morning dose is available are given.     

Application of ninhydrin to spectrophotometric determination of famotidine in drug formulations

A simple and fast spectrophotometric procedure has been developed for the determination of famotidine. The method is based on the interaction of ninhydrin with primary amines present in the famotidine. This reaction produces a blue coloured product which absorbed maximally at 590 nm. The effects of variables such as reagent concentration and reaction time were investigated to optimize the procedure. Beer's law was obeyed in the concentration range of 5-30 microg ml(-1) with molar absorptivity of 6.99 x 10(3) l M(-1) cm(-1). The results were validated statistically. The proposed method has been applied to the determination of famotidine in tablets with satisfactory results.     

Potentiometric determination of acetylsalicylic acid by sequential injection analysis (SIA) using a tubular salicylate-selective electrode

This paper deals with the development of an automated procedure for formulation assays and dissolution tests based on a sequential injection analysis (SIA) system involving an ion-selective electrode as sensing device. Construction of a tubular salicylate (Sal) selective electrode suitable for potentiometric determination of acetylsalicylic acid (Asa) in pharmaceutical formulations is described. The flow-through electrode is formed by a PVC membrane containing 29.2% (w/w) PVC, 5.8% (w/w) tetraoctylammonium salicylate (ionic sensor), 58.5% o-nitrophenyloctylether (plasticizer) and 6.5% (w/w) p-tert-octylphenol (stabilising additive which increases electrode selectivity). The calibration range is 0.05–10 mM Sal, the limit of detection (LOD) is 0.05 mM Sal, the slope is 56.0 mV per decade at 22°C. The R.S.D. is 0.20% (15 readings) when determining 2.5 mM Sal in standard solution. The electrode is used for sensing Asa after its on-line chemical hydrolysis to Sal in a SIA system. The sampling rate is 6 h⁻¹ but for the dissolution tests the frequency is increased to 20 h⁻¹. The SIA set-up is employed for the assay of Asa in plain tablets, composed tablets and effervescent tablets and for performing dissolution tests of normal and sustained release tablets. Results obtained by this technique compare well with those required by the US Pharmacopoeia XXIV.     

Determination of enzyme (angiotensin convertase) inhibitors based on enzymatic reaction followed by HPLC

For determination of levels of plasmatic inhibitor of ACE (angiotensin convertase) a simple method was used based on a combination of enzymatic reaction followed by an HPLC determination of its product. The inhibitor (e.g. enalaprilat) was at first separated from the biological material by deproteination (methanol). Then, an aliquot of the sample was added to the reaction mixture containing a commercial ACE enzyme, its specific substrate FAPGG (N-(3-[2-furyl]acryloyl)-Phe-Gly-Gly) and buffer (Tris–HCl, pH 7.5). Degree of inhibition of the conversion of this substrate to FAP (desGlyGlyFAPGG) by the inhibitor present in the sample is related to its amount by a simple dose–response relationship. The amount of the FAP was determined by an HPLC on a RP-18 column with an acetonitril–nonylamine buffer (pH 2.4, adjusted with phosphoric acid) as a mobile phase with detection at 305 nm. Alternatively, the activity of the endogenous ACE present in the plasma was measured. The substrate FAPGG was added to the plasmatic sample containing both the inhibitor and endogenous ACE (as the sample was not deproteinized in this case) and the reaction product was determined as above. Inhibitor concentration has been obtained from a dose–response curve expressing the interaction with inhibitor with an ACE enzyme.     

经导管封堵对先天性心脏病伴肺动脉高压患者血浆脑钠素的影响及其药物干预研究

目的 探讨经导管封堵术对先心病(congenital heart disease,CHD)伴肺动脉高压(pulmonary arterial hyperten-sion,PAH)患者血浆脑钠素(brain natriuretice peptide,BNP)浓度的影响及依那普利和美托洛尔的干预作用.方法 选择肺动脉收缩压(SPAP)≥50 mmHg的CHD患者119例,分为3组:A组(依那普利组,0.3～0.4 mg·kg-1·d-1,n=44),B组(美托洛尔组,0.8～1.0 mg·kg-1·d-1,n=39),C组(无药物干预,n=36).分别于封堵术前当天及术后第4天、2个月、6个月抽血检测BNP浓度.药物干预组患者自术后第4天抽血后开始服药.另选同期在我院进行健康检者20例为对照组.结果 ①封堵术前,A、B、C 3组血BNP水平比较无明显差异.与对照组比较,3组术前、术后第4天及C组术后2个月血BNP浓度均显著升高(P<0.01).②用药前,A、B、C 3组血BNP水平无明显差异(P>0.05).术后2个月及6个月时,3组患者血BNP浓度均较用药前显著降低(P<0.01);A、B两组以及C组血BNP浓度分别于术后2个月及6个月恢复至对照组水平.③组间比较显示:A、B两组血BNP浓度于术后2个月时较C组显著降低(P<0.05),药物干预后A、B两组间血BNP浓度比较无显著性差异(P>0.05).结论 在介入治疗术后,CHD伴PAH患者的血BNP浓度先升高后降低,依那普利及美托洛尔均有促进其恢复的作用.