紫外分光光度法测定复方苯巴比妥散的含量

在氢氧化钠溶液（０．１ｍｏｌ／Ｌ）中将阿司匹林水解成水杨酸。以ｐＨ９．０缓冲液为溶剂，在２４０ｎｍ和２９７ｎｍ经倍率法测定苯巴比妥，在２９７ｎｍ测定水杨酸间接定量阿司匹林。阿司匹林和苯巴比妥的平均回收率分别为１００．１％和１００．３％；ＲＳＤ为０．５％和０．９％。     

苯巴比妥血药浓度监测61例结果分析

目的：测定苯巴比妥血药浓度。方法：使用ＨＰＬＣ法进行测定。结果：６１例苯巴比妥血药浓度测定结果中,７０．５％在治疗范围,９．８％血药浓度偏高,１９．７％血药浓度偏低。结论：苯巴比妥血药浓度个体差异大,其血药浓度监测在癫痫治疗中具有重要的临床指导意义。     

反相高效液相色谱法测定苯巴比妥血药浓度

目的：建立一种快速测定苯巴比妥血药浓度的方法。方法：采用反相高效液相色谱法,以卡巴西平为内标,测定苯巴比妥血药浓度,钯谱柱ｓｈｉｍａｄｚｕ ｓｈｉｍｐａｃｋＣＬＣ－Ｃ１８不锈钢柱,流动相为甲醇－水（６０：４０）,流速０．８ｍｌ／ｍｉｎ,检测波长２５４ｎｍ。结果：在５～４０ｕｇ／ｍｌ逍度范围内线性良好（ｒ＝０．９９９９）,最低检测限为１１．５７ｎｇ／ｍｌ高、中、低三种浓度的平均回收率分别为１００．２４％,１００．２８％,９９．４１％,ＲＳＤ分别为０．７％,２．７％,５．８％（ｎ＝９）。日内和日间平均ＲＳＤ分别为３．３％,５．２％,８．７％和７．３％。７．３％,９．２％（ｎ＝９）。结论：该方法准确、快速、简便,灵敏度高,重现性好,可作为苯巴比妥血药浓度监测的常规方法。     

反相高效液相色谱法同时测定血浆中氯胺酮,苯巴比妥和阿托品的浓度

本文采用ＺｏｒｂａｘＣ８色谱柱，甲醇－磷酸盐缓冲液（６９∶３１）为流动相，２２０ｎｍ为检测波长，非那西丁为内标，建立了同时测定人血浆中氯胺酮、苯巴比妥和阿托品浓度的反相高效液相色谱法。本法简便、快速、灵敏、重现性好。氯胺酮、苯巴比妥和阿托品的平均回收率分别为９９．２０％，９９．１３％和９７．６２％；不同浓度水平测定结果的日内和日间相对标准偏差均小于５％；其检测限分别为０．２μｇ／ｍｌ，０．０５μｇ／ｍｌ和０．５μｇ／ｍｌ（Ｓ∶Ｎ＝３∶１）。     

反相高效液相色谱法同时测定苯巴比妥和卡马西平血药浓度

目的：建立同时测定微量血浆中苯巴比妥和卡马西平浓度的方法。方法：采用ＲＰ－ＨＰＬＣ法,以艾司唑仑为内标,同时测定微量血浆中苯芭巴比妥和卡马西平浓度。色谱柱ｓｈｉｍａｄｚｕ ｓｈｉｒｍｐａｃｋ ＣＬＣ－Ｃ１８不锈钢柱,流动相为醇－水（６０：４０）,流速０．８ｍｌ．ｍｉｎ＾－１,检测波长２５４ｎｍ。结果：苯巴比妥在４～６０μｇ．ｍｌ＾－１浓度范围内线性良好（ｒ＝０．９９９８）,卡马西平在２～１６μｇ．ｍｌ＾－１浓度范围内线性良好（ｒ＝０．９９９５）,最低检测限分别为１１．５７ｎｇ．ｍｌ＾－１和４．９２ｎｍ．ｍｌ＾－１,两者高、中、低３种浓度的平均回收率分别为９９．９２％,１０１．３０％,９７．９２％和９９．４１％,１０１．５２％,９８．２２％（ｎ＝９）,日内ＲＳＤ分别为３．１％,２．６％,３．８％和１．９％,１．６     

高效液相色谱法测定苯巴比妥血药浓度

苯巴比妥（phenobarbital，PB）为治疗癫痫的有效药物，本文采用HPLC法测定PB血药浓度．ODS色谱技（4.6×250mm），流动相为甲醇－水（40∶60），PB与内标物非那西丁分离较好，保留时间分别为10．7’和13．2’，测定线性范围为1～40μg／ml，最低检测浓度为1μg／ml，平均回收率为101．6％．     

复方苯巴比妥骨架缓释片的制备

目的：研制复方苯巴比妥骨架缓释片，考察其在人工胃液及人工肠液中的溶出情况，为临床合理用药提供参数。方法：将苯巴比妥与硼砂联用，以硬脂酸和乙基纤维素为缓释材料制成复方苯巴比妥骨架缓释片。结果：经体外溶出试验，该片中苯巴比妥在人工胃液中２ｈ累积溶出２１．３８％，在人工肠液中４ｈ累积溶出６２．１５％，６ｈ累积释放达８３．５３％。普通片在人工胃液中４５ｍｉｎ累积溶出７０．１％。结论：实验证明该骨架片与普通片比较具明显缓释作用     

HPLC法测定苯巴比妥东莨菪碱片含量的测量不确定度评价

评价了HPLC法测定苯巴比妥东莨菪碱片含量的测量不确定度。通过不确定度来源分析，建立不确定度的数学模型，并考察测定中的各影响因素。氢溴酸东莨菪碱、苯巴比妥的扩展不确定度分别为2．1％、1．5％，含量测定结果可表示为（108．6±2．1）％、（108．3±1．5）％。     

苯巴比妥预防早产儿脑室内出血的探讨

目的：探讨苯巴比妥预防早产儿脑室内出血的效果。方法：以75例胎龄≤35周的早产儿为观察对象，预防组35例接受苯巴比妥负荷量的平均时龄为生后8，2小时，维持量5天。结果：预防组的脑室内出血发生率（31％）较对照组（46％）显著降低（P〈0．01），同时生后6小时内接受负荷量的脑室内出血发生率（13．6％）较对照组显著降低（P〈0．01）．而生后6小时以后接受负荷量的脑室内出血的发生率（61．5％）较对照组降低不明显。结论：研究显示苯巴比妥可显著降低早产儿脑室内出血的发生率。建议对胎龄≤35周的早产儿生后6小时内常规应用苯巴比妥。以期降低早产儿脑室内出血的发生率。     

高效液相色谱法同时测定苯妥英钠和苯巴比妥血药浓度

目的：建立HPLC法同时测定苯巴比妥和苯妥英钠血药浓度。方法：色谱条件为：以Kromasilc－18柱（5μm）为色谱柱,甲醇-水（57：43）为流动相,检测波长210nm。结果：苯妥英钠平均回收率为99．8％,苯巴比妥的平均回收率为100．7％,RSD不大于5．0％。结论：方法简便,结果准确。     

HPLC法测定阿苯糖丸中阿司匹林和苯巴比妥的含量

目的:建立以高效液相色谱法同时测定阿苯糖丸中阿司匹林和苯巴比妥含量的方法。方法:色谱柱为Inertsil C8-3,流动相为甲醇-0.05mol.L-1磷酸二氢钠缓冲液(50∶50),流速为1.0mL.min-1,检测波长为210nm,柱温为40℃,进样量为20μL。结果:阿司匹林和苯巴比妥检测浓度的线性范围分别为31.15～498.40、3.2～51.2μg.mL-1(r=0.9999);平均加样回收率分别为101.18%(RSD=1.9%)、100.73%(RSD=1.7%)。结论:本方法简便易行、准确可靠,可用于该制剂的质量控制。     

Phenobarbital improves survival in theophylline-intoxicated rabbits

As in humans, theophylline intoxication in rabbits causes seizures and death. We studied whether the administration of phenobarbital or phenytoin following a toxic dose of theophylline would improve survival in rabbits. New Zealand white rabbits were infused intravenously with theophylline, 115 mg/kg over 50 minutes. Upon completion of the infusion, rabbits were randomized to receive either saline (control) (N = 60) or saline containing phenobarbital 20 mg/kg (N = 60), or phenytoin 12 mg/kg (N = 30), infused over 30 minutes. The number (and percentage) of rabbits surviving 24 hours in each group was: control 12 (20%), phenobarbital 30 (50%), and phenytoin 7 (23%) [X2; p less than 0.005; two-tailed]. In all fatal cases, death was preceded by a seizure; rabbits that survived did not seize. These results show that phenobarbital administered intravenously to theophylline-intoxicated rabbits prevented seizures and improved survival whereas phenytoin administration had no significant effect.     

HPLC法测定复方布洛芬干混悬剂中布洛芬及苯巴比妥钠的含量

目的:建立高效相液色谱法测定复方布洛芬干混悬剂中布洛芬及苯巴比妥钠的含量.方法:采用Diammsil C18色谱柱(4.6 mm×150 mm,5 μm),以醋酸钠缓冲液(取醋酸钠6.13 g加水750 mL,振摇使溶解,用冰醋酸调pH为3.0)-乙腈(60:40)为流动相,检测波长为263 nm.结果:布洛芬及苯巴比妥钠的回归方程分别为Y=70.767X-4.536 4,r=0.999 8,Y=111.914X+7.560 1,r=0.999 9,线性关系良好;平均回收率分别为99.98%和99.83%.结论:该方法操作简便,结果准确,可用于复方布洛芬干混悬剂中布洛芬及苯巴比妥钠的含量测定.     

Removal of Phenobarbital During Continuous Cycling Peritoneal Dialysis in a Child

A 2.5-year-old child receiving phenobarbital for a history of seizures while on continuous cycling peritoneal dialysis (CCPD) had persistent subtherapeutic serum levels despite progressive dosage increases. Phenobarbital concentration was measured in the peritoneal dialysate effluent and peritoneal clearance was calculated. Thirty-five percent of the total phenobarbital daily dose was being removed through 24-hour CCPD. Our findings were consistent with previous reports of 40% and 50% phenobarbital removal during continuous ambulatory peritoneal dialysis and acute peritoneal dialysis, respectively. In addition, phenobarbital clearance was greater during the period when more exchanges were done compared with the period when patient went through one cycle with a longer dwell time. Based on these preliminary data, it seems that larger dosages of phenobarbital are necessary in patients undergoing continuous peritoneal dialysis, and that the amount removed can differ significantly depending on the number of cycles.     

Effect of polysorbate 80 on the apparent partition coefficient of drugs and on their intestinal absorption in the rat II. Phenobarbital

The effect of polysorbate 80 on the apparent partition coefficient of phenobarbital between chloroform and a 0.05 M Tris buffer of pH 5.9 were investigated. Three different concentrations of the surfactant were studied; namely 0.001, 0.01 and 1.0% (w/v). The effect of the surfactant in the same medium and at the same concentrations on the absorption of phenobarbital from the rat intestine in situ was also investigated.The apparent partition coefficient of phenobarbital decreased in the presence of polysorbate 80, reaching a minimum at the CMC, then increased markedly at higher concentration.Polysorbate 80 at or below the CMC did not produce a significant effect on the per cent phenobarbital absorbed from the rat intestine in 30 min. Higher concentration of polysorbate 80 produced a significant increase in the per cent absorbed. The mechanisms involved in the effect on apparent partition coefficient as well as on the per cent absorbed are discussed.     

急性鼠药中毒的苯巴比妥疗法

目的:对88例急性鼠药(氟乙酰胺、毒鼠强)中毒导致中枢神经系统功能受损病人进行苯巴比妥疗法,寻找更好的防治措施。方法:两组病人入院后均常规洗胃,使用特效解毒药(乙酰胺、二巯基丙磺酸钠),及时用地西泮、苯巴比妥控制抽搐,昏迷病人佐以脑细胞营养药胞二磷胆碱、纳洛酮治疗。结果:本组88例病人有48例患儿出现抽搐,40例合并多脏器功能衰竭,经综合性治疗82例(93%)治愈,死亡6例(7%)。死亡与毒量大、发病时间长及多脏器功能衰竭等原因有关(P<0.01)。结论:急性鼠药中毒致中枢神经系统功能受损多脏器功能衰竭发生率高在综合治疗基础上佐以苯巴比妥是临床上有效的治疗方法     

The Effect of Valproate on the Metabolism of Phenobarbital in the Rat

Valproate has been shown to interact with all major antiepileptic drugs. The interaction with phenobarbital is the most clinically significant. The mechanism of the interaction was evaluated in the in vivo rat and in vitro liver perfusion system. Phenobarbital and parahydroxyphenobarbital (PbOH) were administered with and without valproate treatment. In vivo, after administration of PbOH, valproate caused a significant inhibition of both the renal clearance of unchanged PbOH (40%) and the formation clearance (ClF) of its glucuronide conjugate (44%). When coadministered with phenobarbital, valproate caused a significant decrease in the total plasma clearance of phenobarbital (95.4 ± 29.0 to 65.8 ± 20.2 ml/hr/kg), with no apparent effect on the phenobarbital renal clearance or the ClF of PbOH. Valproate did cause a significant inhibition (50%) of formation of a minor metabolite, metahydroxyphenobarbital. The largest effect of valproate appears to be on unknown pathways of phenobarbital elimination. In the isolated perfused rat liver, the ClF of PbOH and its glucuronide conjugate were determined. Valproate caused a small (10%) but significant decrease in the ClF of PbOH. As seen in vivo, the most significant effect of valproate was on the ClF of the PbOH glucuronide (66% decrease). In conclusion, inhibition of PbOH formation by valproate cannot account entirely for the increased plasma concentrations of phenobarbital that occur when valproate is added to therapy. A complete understanding of the mechanism will require a complete accounting of the phenobarbital dose in rat or in humans.     

Phenobarbital monitoring in whole blood with a quantitative noninstrumented test

The AccuLevel phenobarbital test is based on enzyme channeling and immunochromatography. AccuLevel is a noninstrumented test for the quantitative determination of phenobarbital concentration in whole blood. Within-run precision data, with 20 replicates at each of five concentrations, has coefficients of variation (CVs) of 4.7-9.2%. Between-run precision (n = 40) results in a CV of 5.9%. The AccuLevel phenobarbital test is very specific and is unaffected by endogenous substances and blood collection tube anticoagulants. Compared to the Emit method, this test has excellent linear correlation for the quantitation of 104 phenobarbital positive patient samples. Reagents stored at 4-8 degrees C are stable for 15 months with no effect on the assay quantitation. This accurate, precise, and specific test is easily performed in 20 min.     

Phenobarbital induces rat liver apolipoprotein A-I mRNA

The effect of phenobarbital on the level of rat liver apolipoprotein A-I (apo-A-I) mRNA was studied. Poly(A+)-RNA isolated from livers of control or phenobarbital-treated rats was translated in vitro in the rabbit reticulocyte lysate system and immunoprecipitated with rabbit antiserum against rat apo-A-I. The immunoprecipitate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The translational activity of apo-A-I mRNA was estimated from the incorporation of [35S]methionine into the apo-A-I band. It was found to be elevated 4-fold by 16 hr after rats received a single injection of phenobarbital. To study the effect of phenobarbital on the level of rat liver apo-A-I mRNA, a recombinant plasmid which contained a cDNA insert corresponding to rat liver apo-A-I mRNA was isolated and used to hybridize total liver poly(A+)-RNA from control and phenobarbital-treated rats. There were 4.8- and 10-fold increases in the amount of hybridization to mRNAs from rats after they were treated with phenobarbital for 8 and 16 hr, respectively. Thus, phenobarbital increases the level of rat liver apo-A-I mRNA.     

Phenobarbital for childhood epilepsy: systematic review

INTRODUCTION: Against a background of concern about the safety of new pharmaceutical products, there has been renewed interest in one of the oldest antiepileptic drugs (AEDs), phenobarbital. Although still in widespread use in developing countries, its popularity has slipped in Western countries over the past century, partly because of controversy about its adverse effect profile. This critical review examines the evidence supporting its effectiveness and its associated behavioural adverse effects for febrile convulsions and childhood epilepsy. METHODS: Relevant randomised controlled trials (RCTs) of phenobarbital vs other antiepileptic drugs or placebo between 1970-2005 were identified through a comprehensive manual and computer database search of the world biomedical literature. Eleven RCTs of febrile convulsions and nine RCTs of childhood epilepsy were systematically reviewed against a conventional set of quality criteria. RESULTS: With a few exceptions, the overall quality of clinical trial methodology, especially in the early studies conducted in the 1970s and 1980s, was poor. There is no evidence for a difference in antiepileptic efficacy between phenobarbital and any other compared AED, yet no evidence for absolute efficacy. No convincing evidence exists for an excess of behavioural adverse effects, over other AEDs, attributable to phenobarbital. Masked studies of phenobarbital in childhood epilepsy have shown no significant differences in behavioural or cognitive adverse effects compared to other AEDs. This is in contrast to the excess of such adverse effects reported in studies open to observer bias. However, the one finding of reduction in cognitive ability associated with phenobarbital treatment for febrile convulsions remains a concern. Future areas of clinical and genetic epidemiological research are outlined.