Journal of pharmacobio-dynamics最新文献_第5页

Species difference and tissue distribution of uridine diphosphate-glucuronyltransferase activities toward E6080, 1-naphthol and 4-hydroxybiphenyl. 尿苷二磷酸-葡萄糖醛基转移酶对E6080、1-萘酚和4-羟基联苯活性的物种差异和组织分布

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.387

T Yoshimura, S Tanaka, T Horie

{"title":"Species difference and tissue distribution of uridine diphosphate-glucuronyltransferase activities toward E6080, 1-naphthol and 4-hydroxybiphenyl.","authors":"T Yoshimura, S Tanaka, T Horie","doi":"10.1248/bpb1978.15.387","DOIUrl":"https://doi.org/10.1248/bpb1978.15.387","url":null,"abstract":"The apparent in vitro kinetic constants of uridine diphosphate-glucuronyltransferase (UDP-GT) activities towards E6080, 1-naphthol (1-N) and 4-hydroxybiphenyl (4-HB) were determined using microsomes, to assess the effect of inducing agents and evaluate species and tissue differences. In rats, the 3-methylcholanthrene and beta-naphthoflavone treatments increased the Vmax app/KM app values for E6080, 13- and 8-fold, and those for 1-N, 1.9- and 1.7-fold, respectively, but did not affect those for 4-HB. Phenobarbital was ineffective on the UDP-GT activity toward E6080. In rats and rhesus monkeys, the intestinal mucosa had higher specific UDP-GT activity toward E6080 than did the liver, and the rank order of the Vmax app/KM app value for E6080 in the intestinal mucosa was rhesus monkey > rat > guinea pig > beagle. In guinea pig, the Vmax app/KM app value for E6080 in the liver was 4 times higher than that in the intestinal mucosa. Both the Vmax app/KM app values for 1-N and 4-HB in the liver of all species studied were higher than those in the intestinal mucosa, and guinea pig liver showed the highest values, while, about the Vmax app for 1-N and 4-HB, beagle liver had the highest values. In the beagle intestinal mucosa, the Vmax app/KM app values for all 3 substrates studied were extremely low.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 8","pages":"387-93"},"PeriodicalIF":0.0,"publicationDate":"1992-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12650108","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: 6

Tissue distribution of intraperitoneally administered (1-->3)-beta-D-glucan (SSG), a highly branched antitumor glucan, in mice. 腹腔注射(1- >3)- β - d -葡聚糖(SSG)，一种高度分支的抗肿瘤葡聚糖，在小鼠体内的组织分布。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.417

M Suda, N Ohno, Y Adachi, T Yadomae

引用次数: 20

Effects of cisapride on gastrointestinal motor activity and gastric emptying of disopyramide. 西沙必利对胃肠运动活动和胃排空的影响。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.395

T Kuroda, Y Yoshihara, H Nakamura, T Azumi, T Inatome, H Fukuzaki, H Takanashi, K Yogo, M Akima

{"title":"Effects of cisapride on gastrointestinal motor activity and gastric emptying of disopyramide.","authors":"T Kuroda, Y Yoshihara, H Nakamura, T Azumi, T Inatome, H Fukuzaki, H Takanashi, K Yogo, M Akima","doi":"10.1248/bpb1978.15.395","DOIUrl":"https://doi.org/10.1248/bpb1978.15.395","url":null,"abstract":"The effects of cisapride on the gastrointestinal contractile activity and pharmacokinetics of disopyramide were determined in beagle dogs and patients with arrhythmia. In the animal experiments, the gastric motor index was significantly decreased by i.v. administration of disopyramide in a dose-dependent fashion. The peak decrease of the motor index was observed within 5 min after i.v. injection of disopyramide; the motor index then recovered gradually to the level present prior to drug administration. I.v. administration of cisapride (0.5 mg/kg) markedly increased gastrointestinal contractile activity following the decrease induced by disopyramide pretreatment (5 mg/kg, i.v.). In the clinical studies, the gastric emptying test was performed using the acetaminophen method. A significant correlation between plasma concentrations of disopyramide and gastric emptying time has been found (p < 0.001). The combination of disopyramide (100 mg t.i.d.) and cisapride (2.5 mg t.i.d.) significantly increased gastric emptying compared with that induced by disopyramide alone. The peak plasma concentration of disopyramide in association with cisapride oral administration was significantly higher, and the apparent absorption rate constant and lag time of disopyramide were about 2-fold higher and 2-fold shorter, respectively, than for disopyramide alone. Cisapride, acting as a cholinergic agonist, may counteract the anticholinergic effect of disopyramide on gastric motility. As a factor influencing drug absorption, gastric emptying is of importance, as it determines the rate of drug delivery to the small intestine. Therefore, the oral administration of disopyramide with cisapride may be useful for patients with delayed gastric emptying.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 8","pages":"395-402"},"PeriodicalIF":0.0,"publicationDate":"1992-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12650109","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: 6

Development of physical dependence on morphine not accompanied with tolerance formation. 对吗啡身体依赖的发展不伴有耐受性的形成。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.443

A Ohta, H Kaneto

引用次数: 4

Percutaneous absorption of pindolol and pharmacokinetic analysis of the plasma concentration. 品多洛尔经皮吸收及血药动学分析。

Journal of pharmacobio-dynamics Pub Date : 1992-07-01 DOI: 10.1248/bpb1978.15.347

T Ogiso, M Iwaki, T Tanino, H Oue

引用次数: 2

Importance of hydrolysis of amino acid moiety in water-soluble prodrugs of disodium cromoglycate for increased oral bioavailability. 水溶性甘氨酸二钠前药氨基酸部分水解对提高口服生物利用度的重要性。

Journal of pharmacobio-dynamics Pub Date : 1992-07-01 DOI: 10.1248/bpb1978.15.339

A Yoshimi, H Hashizume, S Tamaki, H Tsuda, F Fukata, K Nishimura, N Yata

{"title":"Importance of hydrolysis of amino acid moiety in water-soluble prodrugs of disodium cromoglycate for increased oral bioavailability.","authors":"A Yoshimi, H Hashizume, S Tamaki, H Tsuda, F Fukata, K Nishimura, N Yata","doi":"10.1248/bpb1978.15.339","DOIUrl":"https://doi.org/10.1248/bpb1978.15.339","url":null,"abstract":"The relationship between physicochemical properties and oral absorption was investigated in prodrugs for the oral delivery of disodium cromoglycate (DSCG). To improve the lipophilicity of DSCG, various lipophilic moieties were introduced into the twin carboxyl groups. However, this did not lead to improved oral absorption in rabbits because of loss of water solubility, in spite of improved lipophilicity. Water-soluble prodrugs, in which an amino acid was introduced into a hydroxy group by ester linkage in addition to ethyl residues at twin carboxyl groups of DSCG, were synthesized and examined for oral absorption in rabbits and rats. The oral absorption of these prodrugs was affected by the species of amino acids introduced as a water-soluble moiety. Therefore, we examined the relation between the oral absorption of water-soluble prodrugs and the hydrolysis rate of the amino acid moiety. A good linear correlation was obtained between the oral absorption and the hydrolysis rate constant catalyzed by digestive enzymes, trypsin or alpha-chymotrypsin. It was thus concluded that the amino acid moiety of water-soluble prodrugs must be rapidly hydrolyzed to a permeable lipophilic prodrug still possessing the ethyl moiety at twin carboxyl groups in the small intestinal tract for good oral absorption.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 7","pages":"339-45"},"PeriodicalIF":0.0,"publicationDate":"1992-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12619294","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

Are free radicals involved in Ca(2+)-induced membrane damage of mitochondria? 自由基是否参与Ca(2+)诱导的线粒体膜损伤?

Journal of pharmacobio-dynamics Pub Date : 1992-07-01 DOI: 10.1248/bpb1978.15.333

S Kora, M Sado, H Koike, H Terada

引用次数: 2

Proceedings of the 12th Symposium on Medicinal Chemistry. Okayama, December 5-6, 1991. 第十二届药物化学学术研讨会论文集。冈山，1991年12月5日至6日。

Journal of pharmacobio-dynamics Pub Date : 1992-07-01