Pharmaceutica acta Helvetiae最新文献_第10页

Effect of variability in hepatic clearance on the bioequivalence parameters of a drug and its metabolite: simulations using a pharmacostatistical model 肝清除变异性对药物及其代谢物生物等效性参数的影响:使用药物统计模型的模拟

Pharmaceutica acta Helvetiae Pub Date : 1998-08-01 DOI: 10.1016/S0031-6865(98)00008-9

Sara E Rosenbaum

{"title":"Effect of variability in hepatic clearance on the bioequivalence parameters of a drug and its metabolite: simulations using a pharmacostatistical model","authors":"Sara E Rosenbaum","doi":"10.1016/S0031-6865(98)00008-9","DOIUrl":"10.1016/S0031-6865(98)00008-9","url":null,"abstract":"<div>A semi-physiological pharmacostatistical model was developed and used to study the manner in which intra-individual variability in hepatic clearance is transmitted to the area-under the plasma concentration-time curve from zero to infinity (AUC) of a drug and its metabolite. In order to clarify the effects, the model contained no other sources of variability. As the drug's hepatic extraction ratio increased, the coefficient of variation (CV) of the AUC of the drug increased, whereas that of the metabolite decreased. The AUC of the metabolite increased as the drug's non-hepatic clearance increased. In contrast, at low extraction ratios, the CV of the AUC of the drug decreased as the drug's non-hepatic clearance increased. At high extraction ratios, the CV of the AUC of the drug was insensitive to the contributions of other forms of clearance. The results suggest that under certain circumstances, smaller samples sizes could be used in bioequivalence studies for highly variable drugs if the test were based on the metabolite rather than the parent drug.</div>","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"73 3","pages":"Pages 135-144"},"PeriodicalIF":0.0,"publicationDate":"1998-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(98)00008-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20628562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

A simple kinetic method for the assay of nalidixic acid in formulations 一种测定制剂中钠啶酸含量的简单动力学方法

Pharmaceutica acta Helvetiae Pub Date : 1998-08-01 DOI: 10.1016/S0031-6865(98)00017-X

Murad I.H Helaleh

引用次数: 1

Imidazolylpropylguanidines as histamine H2 receptor agonists: 3D-QSAR of a large series 咪唑基丙基胍作为组胺H2受体激动剂:大系列的3D-QSAR。

Pharmaceutica acta Helvetiae Pub Date : 1998-08-01 DOI: 10.1016/S0031-6865(98)00015-6

Stefan Dove, Armin Buschauer

{"title":"Imidazolylpropylguanidines as histamine H2 receptor agonists: 3D-QSAR of a large series","authors":"Stefan Dove, Armin Buschauer","doi":"10.1016/S0031-6865(98)00015-6","DOIUrl":"10.1016/S0031-6865(98)00015-6","url":null,"abstract":"<div>Imidazolylpropylguanidines are potent histamine H2 receptor agonists and act as inotropic vasodilators. A large series of 141 derivatives was tested in the isolated guinea pig atrium and submitted to CoMFA. Since all compounds are full agonists, pD2 values reflect H2 receptor binding. Hydrophobicity was considered as Σf of the variable structural moiety, calculated by the Leo–Hansch method. Preliminary Hansch analysis with Σf, (Σf)2 and indicator variables showed that pD2 additively depends on contributions of certain substructures and has a hydrophobic optimum. For CoMFA, all 3D structures were optimized and aligned. Partial Least Squares analysis of pD2 as function of steric and electrostatic field variables and of Σf and (Σf)2 led to models with r2 of 0.78 with and 0.93 without hydrophobicity. Results indicate a parabolic dependence of pD2 on hydrophobic effects. The 3D distribution of field influences on pD2 suggests a model (shape and electrostatic potential) of the binding site. The role of branching and different substituent effects of a first and a second ring indicate that adequately branched structures induce a conformational change of the binding site enabling a favourable accommodation of the second ring with various substituents.</div>","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"73 3","pages":"Pages 145-155"},"PeriodicalIF":0.0,"publicationDate":"1998-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(98)00015-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20629069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Antihyperlipidemic effect of hydroalcoholic extract, and polyphenolic fraction from Dracocephalum kotschyi Boiss 龙脑水醇提取物和多酚部位的降血脂作用

Pharmaceutica acta Helvetiae Pub Date : 1998-08-01 DOI: 10.1016/S0031-6865(98)00016-8

S Ebrahim Sajjadi , A Movahedian Atar , A Yektaian

引用次数: 99

HPLC determination of the stability of tretinoin in tretinoin–minoxidil solution 高效液相色谱法测定维甲酸-米诺地尔溶液中维甲酸的稳定性

Pharmaceutica acta Helvetiae Pub Date : 1998-08-01 DOI: 10.1016/S0031-6865(98)00014-4

A Zarghi, M Jenabi, A.J Ebrahimian

引用次数: 11

Intersupplier and interlot variability in hydroxypropyl celluloses: implications for theophylline release from matrix tablets 羟丙基纤维素的供应商间和批次间变异:基质片中茶碱释放的影响

Pharmaceutica acta Helvetiae Pub Date : 1998-07-01 DOI: 10.1016/S0031-6865(98)00006-5

Carmen Alvarez-Lorenzo, Elisa Castro, José Luis Gómez-Amoza, Ramon Martı́nez-Pacheco, Consuelo Souto, Angel Concheiro

{"title":"Intersupplier and interlot variability in hydroxypropyl celluloses: implications for theophylline release from matrix tablets","authors":"Carmen Alvarez-Lorenzo, Elisa Castro, José Luis Gómez-Amoza, Ramon Martı́nez-Pacheco, Consuelo Souto, Angel Concheiro","doi":"10.1016/S0031-6865(98)00006-5","DOIUrl":"10.1016/S0031-6865(98)00006-5","url":null,"abstract":"<div>The physical and physicochemical properties of three lots of high-viscosity hydroxypropylcellulose (HPC) (two lots from a Japanese supplier and one lot from a US supplier) were compared. The drug-release properties of theophylline matrix tablets prepared with the different polymers were also investigated. HPCs from the two suppliers showed clear differences in molecular weight, molecular structure, particle size distribution, particle shape, and water affinity. Furthermore, clear differences were observed in the time-course of drug release from tablets made with the different polymers. The differences in basic physical and physicochemical properties of the HPCs affect compression behaviour, the capacity for and time-course of water uptake, and the rheological properties of aqueous dispersions, which explains the observed differences in time-course of drug release. Molecular weight and particle size distribution are particularly important determinants of drug release properties. Abnormally rapid drug release was observed from tablets prepared with relatively small amounts of the highest-molecular-weight highest-particle-size HPC. This result, together with the fact that the time-course of drug release differs markedly between matrix tablets prepared with HPCs that come from different suppliers but that are nominally interchangeable (at least according to the criteria given in the US Pharmacopoeia), suggests that these two properties (mean molecular weight and particle size distribution) are of value for quality control of HPCs destined for use in the manufacture of matrix tablets.</div>","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"73 2","pages":"Pages 113-120"},"PeriodicalIF":0.0,"publicationDate":"1998-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(98)00006-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72802743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Aqueous based polymeric dispersion: Plackett–Burman design for screening of formulation variables of Atenolol Gastrointestinal Therapeutic System 水基聚合物分散体:阿替洛尔胃肠道治疗系统配方变量筛选的Plackett-Burman设计

Pharmaceutica acta Helvetiae Pub Date : 1998-07-01 DOI: 10.1016/S0031-6865(97)00052-6

S.V Sastry, M.A Khan

{"title":"Aqueous based polymeric dispersion: Plackett–Burman design for screening of formulation variables of Atenolol Gastrointestinal Therapeutic System","authors":"S.V Sastry, M.A Khan","doi":"10.1016/S0031-6865(97)00052-6","DOIUrl":"10.1016/S0031-6865(97)00052-6","url":null,"abstract":"<div>Bilayered osmotically controlled Gastrointestinal Therapeutic System of atenolol has been obtained by using cellulose acetate pseudolatex prepared by polymer emulsification method. Various factors such as orifice size, coating thickness, amount and nature of polymeric excipients, and amount of osmotic agent influence the drug release from GITS. Therefore, in the present study a 7-factor, 12-run Plackett–Burman screening design was employed to evaluate the formulation variables for atenolol GITS coated with CA pseudolatex. The variables studied were orifice size, %coating weight gain, amounts of sodium chloride, Polyox® N80 and 303, and Carbopol® 934P and 974P on drug release. The screening design has revealed that orifice size, %coating weight gain and amount of Carbopol® 934P have prominent influence on in-vitro atenolol release. The response variable was cumulative percent atenolol released (Y) in 24 h with constraints on percent release at 2, 6, 12 and 18 h. The polynomial equation obtained was Y24=149.82−0.13X1−0.34X2+0.06X3−0.13X4−0.23X5−76.25X6−2.46X7. The results indicated that the drug release under constrained conditions was influenced by the factors with decreasing order of importance as %coating weight gain>Carbopol® 934P>Polyox® N80>Carbopol® 974P>Polyox® 303>amount of sodium chloride>orifice size.</div>","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"73 2","pages":"Pages 105-112"},"PeriodicalIF":0.0,"publicationDate":"1998-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(97)00052-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20617392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

Studies on 2-benzyloxy-4H-3,1-benzoxazin-4-ones as serine protease inhibitors 2-苄基氧基- 4h -3,1-苯并恶嗪-4-酮丝氨酸蛋白酶抑制剂的研究

Pharmaceutica acta Helvetiae Pub Date : 1998-07-01 DOI: 10.1016/S0031-6865(98)00003-X

Michael Gütschow , Ulf Neumann , Joachim Sieler , Kurt Eger

{"title":"Studies on 2-benzyloxy-4H-3,1-benzoxazin-4-ones as serine protease inhibitors","authors":"Michael Gütschow , Ulf Neumann , Joachim Sieler , Kurt Eger","doi":"10.1016/S0031-6865(98)00003-X","DOIUrl":"10.1016/S0031-6865(98)00003-X","url":null,"abstract":"<div>The class of 3,1-benzoxazin-4-ones includes potent inhibitors of various serine proteases. Structural investigations on three 2-benzyloxy-4H-3,1-benzoxazin-4-ones (1–3) are described with respect to their reactivity to alkaline hydrolysis. The <math><msup><mi></mi><mn>13</mn></msup><mtext>C</mtext><mspace></mspace><mtext>NMR</mtext></math> data of 2-benzyloxy-5-methyl-4H-3,1-benzoxazin-4-one 3 are discussed. This peri substituted compound was subjected to a crystal structure analysis. The heterocyclic skeleton together with the carbonyl oxygen and the methyl carbon is planar, and only small angle distortions occurred. The inhibition of neutrophil serine proteases by 1–3 is reported. The different reactivity of the 5-methyl derivative 3 towards serine proteases is mainly influenced by specific interactions within the active sites. Thus, 3 was found to rapidly acylate human leukocyte proteinase 3 and exhibited a Ki value of 1.8 nM.</div>","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"73 2","pages":"Pages 95-103"},"PeriodicalIF":0.0,"publicationDate":"1998-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(98)00003-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20617391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Syntheses and calcium channel antagonist activity of nifedipine analogues with methylsulfonylimidazolyl substituent 甲基磺酰基咪唑基硝苯地平类似物的合成及钙通道拮抗剂活性

Pharmaceutica acta Helvetiae Pub Date : 1998-07-01 DOI: 10.1016/S0031-6865(98)00004-1

A Shafiee , A.R Dehpour , F Hadizadeh , M Azimi

引用次数: 27

Comparative pharmacokinetic study of a floating multiple-unit capsule, a high-density multiple-unit capsule and an immediate-release tablet containing 25 mg atenolol 阿替洛尔25 mg漂浮多单位胶囊、高密度多单位胶囊和速释片的比较药代动力学研究

Pharmaceutica acta Helvetiae Pub Date : 1998-07-01 DOI: 10.1016/S0031-6865(97)00050-2

Nathalie Rouge , Eric Allémann , Marianne Gex-Fabry , Luc Balant , Ewart T Cole , Pierre Buri , Eric Doelker

{"title":"Comparative pharmacokinetic study of a floating multiple-unit capsule, a high-density multiple-unit capsule and an immediate-release tablet containing 25 mg atenolol","authors":"Nathalie Rouge , Eric Allémann , Marianne Gex-Fabry , Luc Balant , Ewart T Cole , Pierre Buri , Eric Doelker","doi":"10.1016/S0031-6865(97)00050-2","DOIUrl":"10.1016/S0031-6865(97)00050-2","url":null,"abstract":"<div>The purpose of this study was to evaluate the possible advantages of floating and high-density dosage forms and their influence on pharmacokinetic parameters. Atenolol was chosen as a model drug because of its poor absorption in the lower gastrointestinal tract. Three formulations containing 25 mg atenolol, a floating multiple-unit capsule, a high-density multiple-unit capsule, and an immediate-release tablet were compared with respect to estimated pharmacokinetic parameters. The two multiple-unit dosage forms were composed of compressed minitablets and had sustained release properties. The bioavailability of the two gastroretentive preparations with sustained release characteristics was significantly decreased when compared to the immediate-release tablet. The floating minitablets seemed to be retained longer in the stomach than the high-density dosage form. The first atenolol concentration detectable in the plasma and the time to peak Tmax were delayed for the floating dosage form. For the parameters Cmax and AUC0–∞, the lower limit of the 90% confidence interval was outside the bioequivalence range (0.80–1.25). This study showed that it was not possible to increase the bioavailability of a poorly absorbed drug such as atenolol using gastroretentive formulations. Atenolol absorption was delayed and the maximum plasma concentration was diminished.</div>","PeriodicalId":19830,"journal":{"name":"Pharmaceutica acta Helvetiae","volume":"73 2","pages":"Pages 81-87"},"PeriodicalIF":0.0,"publicationDate":"1998-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0031-6865(97)00050-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20617389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 150