Increased Sensitivity to the Anticonvulsant Effect of Valproate in Aging BN/BiRij Rats

The aim of the present investigations was to study the influence of increasing age on the pharmacodynamics of valproate in BN/BiRij rats, applying a threshold for electrically induced localized seizure activity as a measure of the anticonvulsant effect. Seven groups of healthy male BN/BiRij rats were used, aged 3, 6, 12, 19, 25, 31, and 37 months. Individual plasma concentration versus anticonvulsant effect relationships were determined during a continuous intravenous infusion of sodium valproate at a rate of 5.5 mg/min/kg. The infusion was terminated when the anticonvulsant effect intensity had reached the maximum attainable level or at a total infusion time of three hours. A nonlinear relationship between valproate concentration and anticonvulsant effect intensity was observed with no maximal effect in the concentration range up to 1200 mg · L^–1. With increasing age a parallel shift in the concentration versus anticonvulsant effect relationships toward lower concentrations occurred. Thus increasing age appears to be associated with an increased sensitivity to the anticonvulsant effect of valproate.Suzanne Hovinga: Deceased January 30, 1991.     

托吡酯和丙戊酸钠治疗特发性全面性强直阵挛发作的临床疗效比较

目的:探讨中等剂量托吡酯(商品名:妥泰)200mg对特发性全面性强直阵挛(GTCS)发作的疗效。方法:64例GTCS患者分成三组,妥泰单药治疗21例,妥泰联合丙戊酸钠治疗22例,另外21例采用丙戊酸钠治疗作对照。结果:妥泰单药组及联用药组治疗GTCS有效例数明显高于单用丙戊酸钠组,差异显著(P<0.05);同时单用妥泰组与联用丙戊酸钠组疗效相近(P>0.05)。结论:妥泰治疗GTCS疗效优于丙戊酸钠,且妥泰单一用药与联用丙戊酸钠治疗疗效相近。     

Sodium Valproate-lnduced Cardiovascular Abnormalities in the JchlCR Mouse Fetus

Sodium valproate was administered to Jcl:ICR mice in order to evaluate teratogenicity in the cardiovascular system. A single dose of 600mg/kg of sodium valproate was injected intraperitoneally on gestational day 6, 7, 8 or 9. On day 18 of gestation, dams were laparotomized to observe incidence and type of cardiovascular abnormality in live fetuses. Cardiovascular abnormalities were found most frequently in the group treated on day 7, being recognized in 86% of litters (19/22) and in 29% of live fetuses (70/238). Among these, there were 28 cases of transposition of the great arteries, 13 of double outlet right ventricle, 11 of endocardial cushion defect, 9 of ventricular septal defect, 5 of tricuspid atresia, and 4 of hypoplastic left heart syndrome.     

丙戊酸钠静脉滴注治疗偏头痛持续状态

目的评估丙戊酸钠治疗偏头痛持续状态的有效性和安全性。方法我们前瞻性地用静脉滴注丙戊酸钠来治疗偏头痛持续状态,然后比较患者治疗前与出院时视觉模拟评分(VAS)。并比较各种因素(一般情况,累计的丙戊酸钠剂量,合并用药)与治疗之间的关系。结果首次治疗中,26次(74.3%)治疗时患者VAS评分较治疗前减少50%或50%以上。所有治疗中,37次(82.2%)治疗使患者VAS评分较治疗前减少50%或50%以上。患者的性别与治疗反应无关。所有治疗中,合并用药(强痛定,索密通,散粒痛和达宁)和治疗时间与治疗反应呈负相关。仅3例(8.6%)出现短暂性眩晕。结论丙戊酸钠静滴是快速,有效和安全的止痛治疗。它对偏头痛持续状态有效。     

碳酸锂合并丙戊酸钠预防双相障碍复发的研究

目的比较碳酸锂合并丙戊酸钠与单用碳酸锂对预防双相障碍复发的疗效。方法对82例临床康复的双相障碍患者随机分为碳酸锂合并丙戊酸钠组及单用碳酸锂组,合并用药组44例,单用碳酸锂组38例,随访观察2年。结果合并用药组有效率为88.6%,单用碳酸锂组有效率为68.4%,两组比较差异有显著性(P<0.05)。结论碳酸锂合并丙戊酸钠对双相障碍有较好的预防复发作用。     

Influence of aminophylline and strychnine on the protective activity of excitatory amino acid antagonists against maximal electroshock-induced convulsions in mice

Summary Aminophylline reversed the protective action of both, D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid (D-CPP-ene — a competitive NMDA antagonist) and valproate (used as a conventional antiepileptic drug for comparative purposes) against maximal electroshock-induced seizures. The respective ED₅₀ values of aminophylline were 55.7 and 98.4mg/kg i.p. However, aminophylline (up to 100mg/kg i.p.) did not influence the protective efficacy of 1-(4-aminophenyl)-4-methyl-7,8-methyl-enedioxy-5H-2, 3-benzodiazepine (GYKI 52466 — a non-NMDA antagonist). Strychnine affected the protection provided by D-CPP-ene, GYKI 52466, and valproate against maximal electroshock — the ED₅₀ values of strychnine for the reversal of the anticonvulsive effects of D-CPP-ene, GYKI 52466 or valproate were 0.082, 0.35 and 0.28mg/kg s.c., respectively.An involvement of strychnine sensitive glycinergic receptor-mediated events in the mechanism of the anticonvulsive activity of excitatory amino acid antagonists and valproate may be postulated. The ineffectiveness of aminophylline to reduce the anticonvulsive effects of GYKI 52466 may distinguish a new class of antiepileptic drugs offering an advantage over conventional antiepileptics in patients with epilepsy, requiring aminophylline for pulmonary reasons.     

高效液相色谱法测定人血清中丙戊酸钠的含量

建立了ＨＰＬＣ方法测定人血清中丙戊酸钠的药物浓度。采用反相柱和乙腈－水（６０∶４０）作为流动相，庚酸作为内标，血样经提取后，用４－溴甲基－６，７－二甲氧基香豆素衍生化，测定波长设在λＳ３２５ｎｍ和λＲ３９８ｎｍ，内标庚酸的保留时间为４．５７ｍｉｎ，丙戊酸钠的保留时间为５．２１ｍｉｎ，线性范围为２～１５０μｇ／ｍｌ。测定了１０名健康受试者单次口服丙戊酸钠片剂后不同时间的血药浓度。     

丙戊酸钠与尼莫地平治疗偏头痛的疗效比较

目的：观察丙戊酸钠与尼莫地平治疗偏头痛的疗效有否差别。方法：偏头痛１２９例，随机分为丙戊酸钠治疗组６６例（男性１７例，女性４９例；年龄２５±ｓ７ａ），丙戊酸钠开始剂量为０．２ｇ，ｐｏ，ｔｉｄ，以后根据发作频率及程度逐渐增量，最大量１．４ｇ／ｄ，共用３ｍｏ；尼莫地平对照组６３例（男性１８例，女性４５例，年龄２７±６ａ），尼莫地平３０ｍｇ，ｐｏ，ｔｉｄ，共用３ｍｏ。结果：丙戊酸钠组总有效率为８３％。尼莫地平组为８５％，２组无明显差异（Ｐ＞０．０５）．未见严重不良反应。结论：丙戊酸钠与尼莫地平治疗偏头痛安全有效、疗效相似。     

用群体药代动力学预测癫痫儿童丙戊酸钠血药浓度

目的 用群体药代动力(PPK)模型和贝叶斯法预测血药浓度。方法 用癫痫儿童丙戊酸钠PPK模型和USC~*PACK软件中的贝叶斯程序,对100例新癫痫患儿丙戊酸钠的血药浓度进行预测。将预测值与实测值做配对t检验,相关和回归分析,计算平均预测误差、预测误差的百分比、不同预测误差百分比的符合率及其95％可信区间、构成比和评价预测的准确程度。结果 预测值与实测值的相关系数为0.99,P<0.001,线性回归Y_(OBS)=0.99)Y_(PRED),决定系数为0.98,P<0.001;平均预测误差为-0.43μg·mL~(-1),预测误差百分比分别为5％,10％,15％,20％,25％,30％的符合率为62％,74％,82％,85％,89％,93％。结论 PPK模型和贝叶斯法可准确预测丙戊酸钠稳态血药浓度。