维生素B6与苯巴比妥的相互作用

目的：探讨大剂量维生素B6与苯巴比妥的相互作用。方法；分析两例新生儿合并使用大剂量维生素B6后其苯巴比妥后血药浓度低谢速度与群体药学参数的差异。结果：患者苯巴比妥血药浓度低谢速度较群体代谢速度较近一倍。结论：大剂量维生素B6可加快苯巴比妥的代谢速度。     

维生素B6与苯巴比妥药物相互作用

目的：探讨大剂量维生素B6与苯巴比妥药物的相互作用。方法：分析2例新生患儿联合应用大剂量维生素B6后其苯巴比妥血药浓度消除速度与群体药动学参数的差异。结果：新生患儿苯巴比妥血药浓度消除速度较群体代谢速度快近1倍。结论：大剂量维生素B6可加快苯巴比妥的消除速度。     

滥用维生素有害无益

近年来,一些药品广告和一些医学科普杂志对维生素类药物作用的夸大宣传,尤其对维生素C、维生素E、维生素A、维生素D的不确切报道,造成滥用维生素药物的现象日益严重。因此,了解维生素的不良反应相当有必要。 现在有的人把维生素当成补品大量地吃,这是很盲目的,对多数健康人来说没有必要,某些维生素的过量蓄积甚至能发生毒性反应。滥用维生素C 　　1对消化系统：每日口服维生素C超过3g,可引起肠蠕动亢进、腹泻、腹痛、溃疡疼痛加剧,严重时致消化道出血。 　　2对泌尿系统：长期大剂量应用可引起草酸盐结石,对其敏感者可引起高尿酸血症,诱发或加重痛风性关节炎或肾结石。 　　3对血液系统：长期大剂量服用维生素C可促进铁的吸收,能引起高铁红细胞性贫血;还可减少肠道对维生素B12的吸收,使巨幼红细胞性贫血加速恶化;长期大剂量服用后突然停药,可造成反跳性坏血病;每日用量超过5g,可致溶血(葡萄糖 6 磷酸脱氢酶缺乏者,使用治疗量也可发生),重者可致命;大剂量维生素还可引起高钙血症和低钠血症,并降低白细胞的吞噬能力。 　　滥用维生素B1 　　长期大剂量应用维生素B1可引起头痛、疲倦、烦躁、食欲减退、腹泻。肌肉注射给药偶见过敏反应,如药物疹、接触皮炎、荨麻疹、红斑、哮喘等。静脉注射偶见过敏性休克。 　　滥用维生素B6 　　长期大剂量应用维生素B6可致消化道溃疡、癫痫和依赖性症状。国外资料报道,孕妇服用大剂量维生素B6可造成胎儿短肢畸形,其过量的症状表现：抑郁症、头痛、疲倦、腹部胀气、易激动、周围神经炎。 　　滥用维生素A 　　维生素A应用过量可致中毒和死亡,其慢性中毒症状是食欲不振、眼球震颤和复视、骨质增生、关节疼痛、皮肤干燥发痒、毛发脱落等;约50％的急性中毒者可引起颅压升高,出现头痛、头昏、呕吐和视乳头水肿等症状;孕妇应用过量可致胎儿畸形。 　　维生素A还有肝脏毒性反应,可能系应用过量,超过肝解毒功能,造成肝细胞坏死、纤维化和肝硬化。 　　滥用维生素D 　　维生素D应用过量可致中毒反应,如果婴幼儿应用过量,所引起的后果,远比自身佝偻病更为严重。维生素D的毒症状是：食欲不振、恶心、呕吐、持续性腹泻、阵发性腹痛;肝、脾肿大;烦躁、失眠、幻觉、抑郁、脑膜刺激性抽搐、意识障碍,肌张力下降和运动功能障碍;肾浓缩功能障碍;肾结石、蛋白尿、肾功能衰竭;高钙血症(全身血管钙化、高血压、动脉硬化、心律失常)。 　　滥用维生素E 　　长期大量应用维生素E,可引起头痛、眩晕、恶主、腹泻、抑郁、视力模糊、内分泌代谢和性功能紊乱、血栓性静脉炎、凝血酶原降低、三酸甘油酯及胆固醇浓度升高、肺栓塞、高血压和心绞痛加重。 　　维生素C忌与哪些药合用 　　1忌与维生素B2或维生素K3、维生素B12、叶酸合用,可发生氧化还原反应,各自作用减弱或消失。 　　2忌与青霉素G或氨苄西林混合静滴,降效;忌与两性霉素B或万古霉素混合,可产生混浊或沉淀;忌大剂量与庆大霉素合用,可使其抗菌活性降低;忌与丝裂霉素(自力霉素)混合注射,也可发生氧化还原反应,降低药效。 　　3忌与抗凝血药华法林、肝素合用,可减弱其抗凝血作用。 　　4忌与碳酸氢钠、氨茶碱、谷氨酸钠合用,维生素C可被氧化、破坏而失效;维生素C不宜与水解蛋白、胰岛素、异烟肼、氯丙嗪、苯海拉明、普鲁卡因、阿托品在同一容器混合注射。 　　维生素B6慎与哪些药合用 　　1慎与异烟肼合用,长期或大剂量应用异烟肼可致机体维生素B6减少。目前多数学者认为,常规量服用异烟肼1～2个月时,可不必合用维生素B6,长期大剂量服用异烟肼,也只需合用少量维生素B6。 　　2慎与胺碘酮合用,胺碘酮有拮抗维生素B6的作用,故长期应用光敏感性增高。如与维生素B6(每日40～100mg)合用可抑制此不良反应。 　　3慎与左旋多巴合用,因维生素B6是多巴脱羧酶的辅酶,能加速左旋多巴的代谢而影响其疗效。但当左旋多巴与多巴脱羧酶抑制剂卡比多巴联用时,加服维生素B6,反能提高抗震颤麻痹的疗效。 　　4慎与苯巴比妥、苯妥英钠合用,大剂量维生素B6可降低两者的血药浓度     

癫痫患儿苯巴比妥血药浓度的测定及其临床意义

目的探讨影响癫痫患儿体内苯巴比妥的血药浓度的因素。方法用高效液相色谱法检测癫痫患儿体内苯巴比妥的血药浓度。结果癫痫患儿体内苯巴比妥的血药浓度与给药剂量,年龄有关,但是与性别无相关性。结论苯巴比妥的血药浓度受多种因素的影响,在癫痫患儿用药时应把这些因素考虑在内,建立个体化给药方案。     

毒物分析用于1例苯巴比妥中毒患者抢救

目的：为临床提供大剂量苯巴比妥中毒患者血药浓度与临床症状的关系。方法;介绍一例进行中毒药物测定的患者,报告并解释其抢救过程血药浓度与相应的临床症状。结果：中毒患者在血药浓度指导下,成功地采用血液灌流进行抢救。结论：毒物分析能有效指导临床苯巴比妥中毒患者抢救,血药浓度与临床症状密切相关。     

4种常用抗癫痫药物血清与唾液中浓度的测定与相关性研究

癫痫是一种需长期服药控制发作的疾病,卡马西平、苯妥英钠、苯巴比妥、丙戊酸是目前常用的抗癫痫药物,但4种药物个体差异大、治疗窗狭窄,特别是其所具有的药酶诱导作用能够促进自身的代谢[1,2],导致使用剂量与血药浓度、治疗效果相关性的变异,因此需要进行血药浓度的监测以保证对癫痫发作的控制.     

卡马西平、苯妥英钠和苯巴比妥的血药浓度与不良反应及疗效相关性

目的:研究卡马西平、苯妥英钠和苯巴比妥的血药浓度与不良反应及疗效的关系。方法:采用高效液相色谱法同时测定卡马西平、苯妥英钠和苯巴比妥血药浓度。利用Eta系数描述血药浓度与不良反应及疗效的相关性,并采用Logit模型研究血药浓度与不良反应及疗效的关系。结果:卡马西平血药浓度与不良反应及疗效的Eta系数分别为0.558,0.554。苯妥英钠和苯巴比妥血药浓度与不良反应的Eta系数分别为0.977,0.968。结论:卡马西平血药浓度与不良反应及疗效存在相关性。苯妥英钠、苯巴比妥血药浓度与不良反应存在相关性,与疗效相关性弱。这为临床合理用药提供了实验依据。     

维生素B6在肼类火箭推进剂中毒救治中的应用

目的 :对维生素B6 在肼类火箭推进剂中毒救治中的应用进行综述。方法 :文献调研。结果 :维生素B6 是目前火箭推进剂“三肼”中毒救治的特效药 ,研究开发快捷、高效、安全的维生素B6 新剂型或复方制剂 ,对于救治火箭推进剂肼类中毒 ,避免或减少人员伤亡具有十分重要意义。在肼类中毒救治中 ,维生素B6 的长期安全剂量为 5 0 0mg·d- 1,治疗剂量应据个体差异及染毒状况 ,建议先尽快静注 1～ 5 g维生素B6 ,如染毒量大 ,病情重 ,发展快 ,痉挛不止 ,可重复静注维生素B6 0 5～ 1g ,然后改为每 0 5～ 1 0h 0 5 g静滴 ,直到痉挛停止发作。 2 4h内不宜超过 10 g。大剂量维生素B6 可能导致神经系统等方面的严重不良反应。结论 :维生素B6 在肼类火箭推进剂中毒救治中得到了有效、广泛的应用     

大剂量维生素B6对大鼠重型脑外伤后神经细胞凋亡的影响

目的:观察和探讨大剂量维生素B6对大鼠外伤性脑损伤(TBI)后神经细胞凋亡的影响及意义。方法:54只SD雄性大鼠随机分为假手术组、脑损伤对照组,脑损伤大剂量维生素B6治疗组,12h、1d、3d、7d四个时间点,共9组,每组6只。采用Feeney,s自由落体打击法制作重型脑外伤模型,治疗组伤后维生素B6注射液450mg/KG腹腔注射,一天两次,对照组给予等量生理盐水。各时间点检测脑外伤后24h大脑伤灶周围皮层中B细胞淋巴瘤/白血病-2(bcl-2)的表达,原位缺口末端标记法(TUNEL)检测神经细胞的凋亡。结果:大剂量维生素B6治疗后,与脑外伤对照组相比较,1d、3d组可以上调bcl-2的表达,TUNEL阳性细胞减少,即凋亡细胞数减少,具有统计学意义(P0.05)。结论:TBI后应用大剂量维生素B6,能在部分时间段减少神经细胞凋亡,起到神经保护作用。     

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。     

Urinary 6-beta-OH-cortisol and paracetamol metabolites as a probe for assessing oxidation and conjugation of chemicals in humans

The ratio between urinary 6-beta-OH-cortisol and 17-OH-corticosteroids was taken as an indirect estimate of monoxygenase activity in a population of controls and epileptic patients undergoing therapy with diphenylhydantoin and phenobarbital. Cortisol hydroxylation was increased in the group of epileptics with large inter-individual variations notwithstanding a similar dosage of inducers. The levels of some phase II conjugating enzymes were followed by administering paracetamol and measuring the urinary excretion of its main metabolites. Paracetamol glucuronate was increased by levels of cysteine and mercapturic derivatives of paracetamol did not vary, whereas sulfate derivatives were decreased in epileptic patients. Plasma N-acetyl-transferase activity did not vary in either group. Hydroxylated cortisol and paracetamol glucuronide excretion were not correlated in the same individuals, and no correlation was found between the ratio of 6-beta-OH-cortisol/17-OH-corticosteroids and the plasma levels of diphenylhydantoin or phenobarbital. Oxidation of cortisol and conjugation of paracetamol were controlled with different mechanisms, varied considerably between individuals and were not predictive of the pharmacokinetics of the inducers in treated patients.     

The effect of poor compliance on the pharmacokinetics of carbamazepine and its epoxide metabolite using Monte Carlo simulation

Aim:

To study the effects of delayed and missed doses (poor compliance) on the pharmacokinetics of carbamazepine (CBZ) and its main active metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese epilepsy patients using Monte Carlo simulation.

Methods:

CBZ and CBZE time-concentration profiles in various scenarios were generated based on a population pharmacokinetic study in Chinese epilepsy patients using Monte Carlo simulation. The scenarios included patients given multiple doses of CBZ that ranged from 100 to 300 mg three times daily or from 200 to 300 mg every 12 h. The therapeutic range of CBZ and CBZE for each scenario was estimated to assess the effect of delayed or missed doses and to design corresponding rescue regimens. Moreover, the impact of body weight, absorption rate and co-therapy with other antiepileptic drugs (phenytoin, phenobarbital and valproic acid) on the dosage recommendation was investigated in the event of poor compliance.

Results:

The risk for a sub-therapeutic range of CBZ and CBZE was increased in a dose-dependent manner in both two and three times daily regimens when delayed or missed doses occurred. The effects of poor compliance was less prominent on the lower daily doses compared with those on the higher daily doses. The dose recommendations, in the event of poor compliance, were time related and dose dependent. Patient body weight, absorption rate and co-therapy with phenytoin, phenobarbital and valproic acid had no significant impact on the dose recommendation.

Conclusion:

Patients with epilepsy should take the delayed doses as soon as they remember, and partial missed doses may need to be taken near or at the next scheduled time.     

Biopharmaceutics of rectal administration of drugs in man 7. Absorption rate and bioavailability of phenobarbital and its sodium salt from rectal dosage forms

In this report it will be shown that rectal administration of phenobarbital and its sodium salt can be looked upon as an alternative route of administration.Plasma phenobarbital concentrations were measured in 6 volunteers after a single oral dose (219 mg) of sodium phenobarbital and after single rectal doses of phenobarbital (200 mg) or sodium phenobarbital (219 mg). In the case of the rectally administered aqueous dosage forms of phenobarbital no distinct difference in absorption rate occurred whether the sodium salt or the free acid was used. Rectal administration of both types of micro-enemas results in absorption which is less rapid than after oral administration of the sodium salt. However, the final and total absorption of phenobarbital and its sodium salt after 6.5 h is practically complete, compared with oral administration. The in vitro release of phenobarbital from fatty suppositories using a coarse powder (125–250 μm) of sodium phenobarbital and with a fine powder (<20 μm) of phenobarbital showed marked differences. The rectal absorption profile of the aqueous and fatty dosage forms of sodium phenobarbital in vivo was quite similar. A much slower absorption rate was observed if the free acid was used in the fatty suppository dosage form.     

Effect of smoking on single dose pharmacokinetics of phenobarbital

In order to determine interaction of smoking with single dose pharmacokinetics of phenobarbital, a 60 mg tablet of the drug was given to 12 healthy male subjects in two groups (6 smokers and 6 non-smokers) in a double blind study. An HPLC method using UV detection was developed to assess phenobarbital in plasma of the subjects. Pharmacokinetic parameters were calculated and compared in the two groups. Pharmacokinetic parameters of the two groups were not significantly different in the two groups (p<0.05). The results show no considerable effect of cigarette smoking on phenobarbital pharmacokinetics, which is in agreement with enzyme studies performed previously.     

The disposition of valpromide in rats and the isolated perfused rat liver

The pharmacokinetics and metabolism of valpromide (VPD) were investigated in intact rats and in the isolated perfused rat liver (IPL). The rats and the IPLs were divided into three groups. One was a control (untreated) group. The second consisted of intact rats and IPLs obtained from rats pretreated with phenobarbital. A third group of rats received VPD by oral administration. VPD was partially hydrolyzed to valproic acid (VPA) by the IPL following iv administration to intact rats. The fraction of the total body clearance of VPD which furnished VPA as a metabolite (fm) in the rats was 63%. The rate and extent of this conversion were greater in the phenobarbital-pretreated rats and in the IPLs than in the control group. Our studies showed that phenobarbital can induce the hydrolytic biotransformation of VPD to VPA. This is in addition to its known effect on oxidative metabolic pathways. In rats, as in humans and dogs, VPD is biotransformed to VPA in the liver. The complete oral bioavailability of VPD and the fact that the AUC of VPA obtained after oral administration of VPD was not higher than that obtained after the iv injection of VPD indicates that the gastrointestinal tract is not one of the metabolic sites of VPD to VPA conversion.     

Isoniazid overdose : a case series, literature review and survey of antidote availability

Tuberculosis has re-emerged as a significant public health threat over the last decade both globally and within Australia. This is thought to be largely due to the HIV epidemic, a growing itinerant population, and immigration. The antibiotic isoniazid remains an integral part of drug therapy. With the numbers of patients receiving isoniazid remaining high, the number of cases of acute poisoning is expected to be significant. This paper presents a series of two cases of isoniazid poisoning presenting to a tertiary referral centre in North Queensland. Isoniazid toxicity produces a triad of coma, metabolic acidosis and seizures. The seizures are often refractory to traditional antiepileptics. A specific antidote is available (pyridoxine [vitamin B6]) and both patients were administered this as part of their treatment. We also surveyed all hospitals in Australia with an accredited adult Emergency Department to assess the availability of pyridoxine.     

Different pharmacokinetics of dichlorofluoromethane (CFC 21) and chlorodifluoromethane (CFC 22)

Inhalation pharmacokinetics of dichlorofluoromethane (CFC 21) and chlorodifluoromethane (CFC 22) were studied in male Wistar rats by use of a closed inhalation chamber system. CFC 21 was readily eliminated via metabolism.However, CFC 22 underwent no detectable metabolism; pretreatment of the rats with DDT or phenobarbital did not stimulate metabolic transformation of the compound. Hence, formation of biologically relevant amounts of reactive intermediates from CFC 22 as a mechanism of toxicity seems unlikely.     

Potentiation of pyridoxine by depressants and anticonvulsants in the treatment of acute isoniazid intoxication in dogs

Treatments for acute isoniazid (INH) intoxication have included, singly and in various combinations, a great variety of drugs. As a consequence it is difficult to evaluate the efficacy of these antidotes, except for pyridoxine, the most commonly recommended one. In some cases of INH poisoning evaluation is further complicated because of concurrent alcohol ingestion. The objectives of this investigation were to determine whether ethanol enhances the toxic effects of acute INH overdose, as suggested by some clinical reports, and to evaluate the antidotal efficacy of phenobarbital, pentobarbital, phenytoin, ethanol, or diazepam when each is administered in combination with pyridoxine. Male dogs were either pretreated with iv ethanol and challenged 1 hr later with po INH, 50 or 75 mg/kg, or they were given INH, 75 mg/kg, and injected iv 30 min later with the test drugs, alone or in combination with pyridoxine. Ethanol pretreatment not only did not enhance the toxicity of INH but, in fact, it reduced the severity of convulsions, although it did not change the mortality rate. In the antidotal study, none of the five CNS depressants or anticonvulsants protected against clonic-tonic seizures or death. Pyridoxine, however, reduced the severity of the seizures and prevented death, although it did not completely block convulsions. The combination antidotal treatments (pyridoxine plus each of the CNS drugs) were the most effective; they prevented both convulsions and lethality. It is suggested that pyridoxine is the basic antidote for treatment of acute INH poisoning, and that the addition of an anticonvulsant or a CNS depressant to the therapy enhances effectiveness.     

片仔癀茵胆平肝胶囊对小鼠镇静催眠的作用

目的：研究片仔癀茵胆平肝胶囊的镇静催眠作用，方法：采用小鼠抖笼滴水法，强迫游泳的不动时间和阈下剂量催眠法，结果：片仔癀茵胆平肝胶囊能显著抑制小鼠的自发活动，延长小鼠强迫游泳的不动时间和增加苯巴比妥钠阈下剂量的催眠百分率。结论：片仔癀茵胆平肝胶囊具有镇静和对催眠的协同作用。     

多黏菌素B在重症感染患者中的群体药动学研究

目的 建立多黏菌素B在重症感染患者中的群体药动学模型,为个体化给药提供科学依据。方法 检索PubMed、Embase、Web of Science、CNKI数据库中关于静脉滴注多黏菌素B的药动学文献,提取多黏菌素B在重症感染患者中的药动学数据,使用Monolix软件建立多黏菌素B的群体药动学模型,并对模型进行图形评价和Bootstrap法验证。结果 多黏菌素B在重症感染患者中的药动学特性符合房室模型,多黏菌素B的清除率（CL）、中央室表观分布容积（V1）、周边室表观分布容积（V2）、隔间清除率（Q）的群体典型值分别为4.36 L/h、16.19 L、35.14 L、0.4 L/h,患者的年龄对模型参数Q有显著影响,模型评价表明模型稳定,且有较好的预测效能。结论 本研究建立了重症感染患者多黏菌素B的群体药动学模型,可为多黏菌素B在成年重症感染患者中的个体化用药提供参考。