Pharmaceutisch weekblad. Scientific edition最新文献_第6页

Pharmacological, toxicological and neurochemical effects of delta 2(E)-valproate in animals. δ 2(E)-丙戊酸对动物的药理学、毒理学和神经化学作用。

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-06-19 DOI: 10.1007/BF01962706

P E Keane

引用次数: 1

Pharmacological, toxicological and neurochemical effects of delta 2(E)-valproate in animals. δ 2(E)-丙戊酸对动物的药理学、毒理学和神经化学作用。

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-06-19 DOI: 10.1007/BF01962705

W Löscher

{"title":"Pharmacological, toxicological and neurochemical effects of delta 2(E)-valproate in animals.","authors":"W Löscher","doi":"10.1007/BF01962705","DOIUrl":"https://doi.org/10.1007/BF01962705","url":null,"abstract":"The E isomer of 2-ene-valproic acid (delta 2(E)-VPA) is the major active metabolite of the antiepileptic drug valproate (VPA) in various species, including humans. Experimental studies on delta 2(E)-VPA and VPA indicate that delta 2(E)-VPA may be a useful antiepileptic drug itself. delta 2(E)-VPA has the same wide spectrum of anticonvulsant activity as VPA with a somewhat higher anticonvulsant potency in rodent and dog models of different seizure types. As VPA, delta 2(E)-VPA increases presynaptic gamma-aminobutyric acid (GABA) levels in the brain, presumably by an effect on GABA synthesis and/or GABA degradation. delta 2(E)-VPA is a much more potent inhibitor of the human brain GABA-degrading enzyme than VPA. In high doses delta 2(E)-VPA is more sedative in rodents than is VPA; LD50 values are about the same. In mouse and rat models for teratogenicity, delta 2(E)-VPA does not induce teratogenic effects, whereas VPA is teratogenic in these models. Pilot rat studies on liver toxicity of VPA and VPA metabolites suggest that delta 2(E)-VPA is not hepatotoxic. In view of the rare but serious hepatotoxicity and teratogenicity of VPA in humans, delta 2(E)-VPA obviously merits interest as a valuable alternative drug in antiepileptic therapy.","PeriodicalId":19804,"journal":{"name":"Pharmaceutisch weekblad. Scientific edition","volume":"14 3A","pages":"139-43"},"PeriodicalIF":0.0,"publicationDate":"1992-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01962705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12670717","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: 7

Studies on 2-n-propyl-2(E)-pentenoate (delta 2(E)-valproate) in man. 人体内2-n-丙基-2(E)-戊酸酯(2(E)-丙戊酸酯)的研究。

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-06-19 DOI: 10.1007/BF01962709

L Gram

引用次数: 0

Enzymes involved in the metabolism of valproate. 丙戊酸酶与丙戊酸代谢有关的酶

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-06-19 DOI: 10.1007/BF01962696

J Hulsman

引用次数: 3

Effects of valproate on xenobiotic biotransformation in rat liver. In vivo and in vitro experiments. 丙戊酸酯对大鼠肝脏外源性生物转化的影响。体内和体外实验。

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-06-19 DOI: 10.1007/BF01962703

V Rogiers, A Callaerts, A Vercruysse, M Akrawi, E Shephard, I Phillips

{"title":"Effects of valproate on xenobiotic biotransformation in rat liver. In vivo and in vitro experiments.","authors":"V Rogiers, A Callaerts, A Vercruysse, M Akrawi, E Shephard, I Phillips","doi":"10.1007/BF01962703","DOIUrl":"https://doi.org/10.1007/BF01962703","url":null,"abstract":"Male Wistar rats were in vivo exposed for 2 weeks to 100 micrograms/ml sodium valproate by subcutaneous implantation of osmotic pumps and hepatocytes were isolated. As an in vitro model co-cultures of rat hepatocytes with epithelial cells were daily treated with valproate (25, 50, 100, 200 micrograms/ml) for 2 weeks. In both models the cytochrome P-450 content and the enzymatic activities of 7-ethoxycoumarin O-deethylase, aldrin epoxidase and glutathione S-transferase were determined in valproate-treated hepatocytes, in controls and in phenobarbital-induced cells. It appeared that in both systems the cytochrome P-450 content and the 7-ethoxycoumarin O-deethylase activity increased significantly after valproate treatment. On the other hand, the activities of aldrin epoxidase and glutathione S-transferase decreased. A cDNA probe, encoding rat P450IIB2 was used to determine whether mRNAs encoding the P450IIB subfamily were induced by valproate. It became clear that the inducing effect of valproate was even more pronounced in vitro than in vivo.","PeriodicalId":19804,"journal":{"name":"Pharmaceutisch weekblad. Scientific edition","volume":"14 3A","pages":"127-31"},"PeriodicalIF":0.0,"publicationDate":"1992-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01962703","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12670715","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: 9

Single-dose tolerance and pharmacokinetics of 2-n-propyl-2(E)-pentenoate (delta 2(E)-valproate) in healthy male volunteers. 健康男性志愿者2-n-丙基-2(E)-戊酸酯(δ 2(E)-丙戊酸酯)的单剂量耐受性和药代动力学

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-06-19 DOI: 10.1007/BF01962708

R H Düsing

引用次数: 3

Metabolism of valproate to hepatotoxic intermediates. 丙戊酸代谢为肝毒性中间体。

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-06-19 DOI: 10.1007/BF01962701

T A Baillie

引用次数: 22

Pharmacokinetics of valproate in pregnancy: mother-foetus-newborn. 丙戊酸在妊娠期的药代动力学:母亲-胎儿-新生儿。

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-06-19 DOI: 10.1007/BF01962699

S I Johannessen

{"title":"Pharmacokinetics of valproate in pregnancy: mother-foetus-newborn.","authors":"S I Johannessen","doi":"10.1007/BF01962699","DOIUrl":"https://doi.org/10.1007/BF01962699","url":null,"abstract":"An increased risk of seizures during and immediately after labour has been observed in epileptic women, and it is recognized that serum levels of antiepileptic drugs may decrease in pregnancy. Several studies have suggested that total valproate levels fall, but that free fractions increase during pregnancy. Recent findings suggest that the actual metabolism of valproate is not altered by pregnancy and that the changes of the plasma clearance are due primarily to decreased protein binding. The levels of free drug will not change significantly as pregnancy advances. However, dose reduction after delivery may be necessary to avoid toxicity. Valproate and its metabolites undergo placental transfer. In the foetus the plasma level of valproate and the protein binding are higher than in maternal plasma, and the half-life of valproate following placental transfer is considerably longer than in adults. Only small amounts of valproate appear in breast milk and those are not likely to cause any problems. During pregnancy and the first month after delivery preferably both total and free valproate serum levels should be closely monitored to determine the lowest effective dose.","PeriodicalId":19804,"journal":{"name":"Pharmaceutisch weekblad. Scientific edition","volume":"14 3A","pages":"114-7"},"PeriodicalIF":0.0,"publicationDate":"1992-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1007/BF01962699","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12671628","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: 14

Platinum antitumour agents: a review of (bio)analysis. 铂类抗肿瘤药物:生物分析综述。

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-06-19 DOI: 10.1007/BF01962689

T J Hodes, W J Underberg, G Los, J H Beijnen

引用次数: 6

Acitretin (Neotigason). A review of pharmacokinetics and teratogenicity and hypothesis on metabolic pathways. Acitretin (Neotigason)。药代动力学、致畸性及代谢途径假说综述。

Pharmaceutisch weekblad. Scientific edition Pub Date : 1992-04-24 DOI: 10.1007/BF01980479

M L Bouvy, M C Sturkenboom, M C Cornel, L T De Jong-Van den Berg, B H Stricker, H Wesseling

引用次数: 2