Journal of pharmacobio-dynamics最新文献_第4页

Single-dose kinetics of primidone in human subjects: effect of phenytoin on formation and elimination of active metabolites of primidone, phenobarbital and phenylethylmalonamide. 人体内普米酮的单剂量动力学:苯妥英对普米酮、苯巴比妥和苯乙基丙二胺活性代谢物形成和消除的影响。

Journal of pharmacobio-dynamics Pub Date : 1992-09-01 DOI: 10.1248/bpb1978.15.467

J Sato, Y Sekizawa, A Yoshida, E Owada, N Sakuta, M Yoshihara, T Goto, Y Kobayashi, K Ito

{"title":"Single-dose kinetics of primidone in human subjects: effect of phenytoin on formation and elimination of active metabolites of primidone, phenobarbital and phenylethylmalonamide.","authors":"J Sato, Y Sekizawa, A Yoshida, E Owada, N Sakuta, M Yoshihara, T Goto, Y Kobayashi, K Ito","doi":"10.1248/bpb1978.15.467","DOIUrl":"https://doi.org/10.1248/bpb1978.15.467","url":null,"abstract":"Effect of repetitive administration of phenytoin (PHT) on the single-dose pharmacokinetics of primidone (PRM) was investigated in 3 healthy male subjects. The peak concentration of unchanged PRM was achieved at 12 and 8 h after the administration of PRM in the absence and the presence of PHT, respectively. The elimination half-life of PRM was decreased from 19.4 +/- 2.2 (mean +/- S.E.) to 10.2 +/- 5.1 h (p < 0.05) and the total body clearance was increased from 24.6 +/- 3.1 to 45.1 +/- 5.1 ml/h/kg (p < 0.01) in the presence of PHT. No significant change was observed for the apparent volume of distribution between the two treatments. In the absence of PHT, the measurable amount (> or = 0.1 mumol/l) of phenobarbital (PB) and phenylethylmalonamide (PEMA) did not appear in the serum until 5.3 and 1.3 h after the PRM administration, and the peak concentrations of PB and PEMA were achieved at 52 and 36 h, but the concentrations of both metabolites were very low (PB 1.3 mumol/l; PEMA 1.7 mumol/l). In the presence of PHT, within 0.8 and 0.5 h after the administration of PRM, the derived PB and PEMA appeared in the serum. About a 6-fold increase in the peak concentrations of both the metabolites were observed (PB 8.2 mumol/l; PEMA 11.0 mumol/l). No significant changes were observed for the elimination half-lives of both PB and PEMA in the absence and presence of PHT.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 9","pages":"467-72"},"PeriodicalIF":0.0,"publicationDate":"1992-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12461408","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: 8

Evaluation of a new penetration enhancer 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101). 新型穿透增强剂1-[2-(癸基硫)乙基]氮杂环戊烷-2- 1 (HPE-101)的评价。

Journal of pharmacobio-dynamics Pub Date : 1992-09-01 DOI: 10.1248/bpb1978.15.527

T Yano, N Higo, K Furukawa, M Tsuji, K Noda, M Otagiri

{"title":"Evaluation of a new penetration enhancer 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101).","authors":"T Yano, N Higo, K Furukawa, M Tsuji, K Noda, M Otagiri","doi":"10.1248/bpb1978.15.527","DOIUrl":"https://doi.org/10.1248/bpb1978.15.527","url":null,"abstract":"A new compound, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101) was synthesized, and its skin penetration enhancing activity was examined by using 14C-indomethacin as a penetrant. A solution of HPE-101 and indomethacin was applied to a cloth pad affixed onto an adhesive tape to give a HPE-101 patch, and the patch was applied to hairless mouse skin. The amount of percutaneously absorbed indomethacin was determined by measuring the radioactivity excreted in urine for 24 h after application. 1) Azone and decylmethyl sulfoxide, enhanced markedly the percutaneous absorption of indomethacin when the propylene glycol-ethanol (9:1 v/v) mixture was used as the solvent. 2) Among various penetration enhancers dissolved in the indomethacin solutions and applied to screen for penetration enhancing activity, HPE-101 was found to be the most prominent. 3) Solvents containing more than 3% (w/w) of HPE-101 produced a plateau level of the penetration enhancing activity. 4) Daily application of 1% (w/w) solutions of HPE-101 or Azone increased the daily excretion of indomethacin significantly above the level excreted on the previous day. However, repeated daily application beyond 3 d gave a steady state excretion of indomethacin. 5) The mouse skin was pretreated with 3% (w/w) solutions of HPE-101 or Azone for 24 h on the 1st day, and the indomethacin solution was applied for 24 h on the 3rd day and 7th day to examine the recovery of skin barrier function. Enhanced excretion of indomethacin was still noted on the 3rd day, but enhancement was not observed on the 7th day.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 9","pages":"527-33"},"PeriodicalIF":0.0,"publicationDate":"1992-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.527","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12461415","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: 16

Pharmacokinetics of zonisamide; saturable distribution into human and rat erythrocytes and into rat brain. 唑尼沙胺药动学研究饱和分布于人和大鼠红细胞和大鼠脑内。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.409

K Nishiguchi, N Ohnishi, S Iwakawa, J Yagi, S Nakayama, S Takada, H Nakamura, T Yokoyama, K Okumura

引用次数: 20

Homology of an acrosome-reacted sperm-specific antigen to CD46. 顶体反应的精子特异性抗原与CD46的同源性。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.455

M Okabe, X Ying, M Nagira, M Ikawa, Y Kohama, T Mimura, K Tanaka

引用次数: 29

Chronopharmacological study of valproic acid in mice: comparison of oral and rectal administration. 丙戊酸对小鼠的时间药理学研究:口服和直肠给药的比较。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.403

Y Yoshiyama, S Nakano, S Ohdo, N Ogawa

{"title":"Chronopharmacological study of valproic acid in mice: comparison of oral and rectal administration.","authors":"Y Yoshiyama, S Nakano, S Ohdo, N Ogawa","doi":"10.1248/bpb1978.15.403","DOIUrl":"https://doi.org/10.1248/bpb1978.15.403","url":null,"abstract":"This study was performed to investigate the influence of the dosing route on chronopharmacological aspect of valproic acid (VPA) in mice, comparing the oral and rectal route. ICR male mice, housed under a standardized light-dark cycle (lights on from 0700 to 1900), were orally or rectally administered 400 mg/kg VPA each at the following scheduled time: 0900, 1300, 1700, 2100, 0100 and 0500. VPA concentrations in plasma and brain were determined by gas-liquid chromatography. There was a circadian rhythm in the electroshock seizure (ES) threshold 30 min after oral VPA administration, with the highest value at the midlight (1300) and the lowest at the middark (0100) (p < 0.01). A significant circadian rhythm was also found in plasma and brain VPA concentrations 30 min after oral administration (p < 0.01). This finding is related to the rhythm in the ES threshold. In contrast to oral administration, no circadian rhythm in the ES threshold, plasma and brain VPA concentrations was observed after rectal administration. These values after rectal dosing showed higher levels in comparison to those after oral dosing. Thus, the rectal route for VPA might have merit to eliminate the time-dependent changes in VPA pharmacologic action and kinetics. The timing of drug administration is an important factor that must be carefully controlled in drug pharmacokinetic and pharmacodynamic studies and must be considered in planning dosing routes.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 8","pages":"403-8"},"PeriodicalIF":0.0,"publicationDate":"1992-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12650110","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: 4

Inhibition of hepatic drug biotransformation by carrageenan-induced inflammation in the rat: effect of sex hormone alterations. 卡拉胶诱导的炎症对大鼠肝脏药物生物转化的抑制作用:性激素改变的影响。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.367

M Ishikawa, K Sasaki, M Ozaki, Y Takayanagi, K Sasaki

{"title":"Inhibition of hepatic drug biotransformation by carrageenan-induced inflammation in the rat: effect of sex hormone alterations.","authors":"M Ishikawa, K Sasaki, M Ozaki, Y Takayanagi, K Sasaki","doi":"10.1248/bpb1978.15.367","DOIUrl":"https://doi.org/10.1248/bpb1978.15.367","url":null,"abstract":"Following in vivo treatment with carrageenan, sex-related differences in alteration of hepatic drug metabolism were found in the rat. In adult male rats, marked decreases were observed in hepatic 9000 x g supernatant cytochrome P-450 content and in the biotransformation of hexobarbital, aminopyrine, ethylmorphine, and meperidine. Hexobarbital hypnosis was significantly prolonged by carrageenan treatment in intact and testectomized animals as compared to their respective controls. Although carrageenan-treated intact animals slept 480% longer, carrageenan-treated testectomized rats slept only 60% longer than the respective control animals. However, testectomy or administration of 17 beta-estradiol to testectomized male rats did not inhibit the monooxygenase activities by carrageenan-treatment. Furthermore, administration of testosterone to ovariectomized female rats did not antagonize the inhibitory effects of the carrageenan-induced inflammation. The inhibitory effects produced by carrageenan-induced inflammation on the microsomal enzyme system were observed only in mature male rats and were not observed in mature female rats or in sexually immature rats of either sex. Thus, these results suggest that the inhibitory effects of carrageenan-induced inflammation on hepatic 9000 x g supernatant monooxygenases in the male rat are partially mediated through the toxic action of carrageenan-induced inflammation on androgen-dependent factors in this enzyme system.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 8","pages":"367-76"},"PeriodicalIF":0.0,"publicationDate":"1992-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.367","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12650104","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: 1

Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. 硒对小鼠肝混合功能氧化酶的抑制作用。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.377

M Ishikawa, M Sasaki, K Koiwai, M Ozaki, Y Takayanagi, K Sasaki

{"title":"Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium.","authors":"M Ishikawa, M Sasaki, K Koiwai, M Ozaki, Y Takayanagi, K Sasaki","doi":"10.1248/bpb1978.15.377","DOIUrl":"https://doi.org/10.1248/bpb1978.15.377","url":null,"abstract":"The effect of selenium administered acutely or chronically on the hepatic microsomal drug-metabolizing system has been investigated in mice. After 72 h following acute administration of selenium (7.5 mg/kg, i.p.), there was a significant inhibition of the activities of aminopyrine (AM) N-demethylase and ethylmorphine (EM) N-demethylase, and cytochrome P-450 levels but no change in the activities of aniline (AN) hydroxylase, 7-ethoxycoumarin (EC) O-deethylase, reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase and reduced nicotinamide adenine dinucleotide (NADH)-ferricyanide reductase, and cytochrome b5 content. Chronic administration of selenium in the drinking water (1 or 2 ppm selenium) for 12 weeks, resulted in no alteration in any of the parameters measured. However, significant decreases in activities of AM N-demethylase and AN hydroxylase, and cytochrome P-450 levels were detected in animals given higher doses of selenium (4 or 8 ppm selenium). Following the in vitro additions of selenium to hepatic microsomes obtained from untreated mice, selenium inhibited the AM N-demethylase, AN hydroxylase and 7-EC O-deethylase in a concentration-dependent manner, but no alteration in NADPH-cytochrome c reductase and cytochrome P-450 levels was observed. These results indicate that selenium is a specific from inhibitor of hepatic monooxygenase.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 8","pages":"377-85"},"PeriodicalIF":0.0,"publicationDate":"1992-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12650105","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: 4

Effect of adenosine 3',5'-cyclic monophosphate derivatives on acute liver injury induced by carbon tetrachloride. 腺苷3′，5′-环单磷酸衍生物对四氯化碳急性肝损伤的影响。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.449

M Saito, A Nasu, S Kataoka, N Yamaji, A Ichikawa

引用次数: 2

Evidence of direct conversion of testosterone sulfate to estradiol 17-sulfate by human placental microsomes. 人胎盘微粒体直接将硫酸睾酮转化为硫酸雌二醇17的证据。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.427

T Satoh, K Watanabe, K Takanashi, S Itoh, H Takagi, I Yoshizawa

引用次数: 9

Direct modulation of secretin binding sites by gastrin in the rat stomach. 胃泌素对大鼠胃分泌素结合位点的直接调节。

Journal of pharmacobio-dynamics Pub Date : 1992-08-01 DOI: 10.1248/bpb1978.15.437

S Iwakawa, H Nomura, R Hori, K Okumura

引用次数: 1