CYP2C19*3基因多态性对癫痫患者奥卡西平活性代谢产物MHD浓度的影响

目的：分析CYP2C19*3基因多态性与癫痫患者奥卡西平（oxcarbazepine，OXC）活性代谢产物10，11-二氢-10-羟基卡马西平（monohydroxycarbazepine，MHD）血药浓度的相关性。方法：纳入120例OXC单药治疗1个月以上且症状控制良好的癫痫患者，采集清晨服药前空腹血，采用高效液相色谱法测定MHD稳态谷浓度。通过PCR和sanger测序判定患者CYP2C19*3基因型。结果：120例癫痫患者快代谢患者64例，MHD血浆浓度为（18.17±7.34）μg·mL^-1；中代谢型患者36例，MHD血浆浓度为（19.31±9.17）μg·mL^-1；慢代谢型患者20例，MHD血浆浓度为（25.79±7.51）μg·mL^-1，3种基因型的MHD浓度有显著性差异（F=7.077，P=0.0013）。多因素分析显示，日剂量作为影响血药浓度的重要指标呈现出显著相关性（P<0.05）。结论：CYP2C19*3基因多态性影响MHD血药浓度，并且日剂量越高，MHD血药浓度越大，两者成显著正相关，临床应进行血药浓度监测。     

RP-HPLC法同时测定人血浆中左乙拉西坦、奥卡西平及其活性代谢产物的浓度

目的：建立同时测定人血浆中左乙拉西坦、奥卡西平及其代谢产物单羟基卡马西平的含量测定方法,为左乙拉西坦与奥卡西平联合用药治疗癫痫提高临床疗效与用药安全性提供指导。方法：患者血浆样品经乙酸乙酯-二氯甲烷（70：30）沉淀蛋白处理后,以β-萘酚做内标,采用RP-HPLC法同时测定左乙拉西坦、奥卡西平及单羟基卡马西平的含量。色谱柱为Agilent C₁₈反相色谱柱,流动相为：乙腈（A）-水相（B）（由0.3%三氟乙酸与10 mmol·L^-1甲酸铵溶液按2：1体积比混合）梯度洗脱,流速1 mL·min^-1,柱温30℃,进样量10 μL,内标为β内萘酚,检测波长为210 nm （0~13 min）、225 nm （13~25 min）。结果：LEV、OXC、MHD血药浓度分别在2.0~60.0、2.0~60.0、3.0~96.0 μg·mL^-1范围内线性关系良好（r分别为LEV 0.999 7、MHD 0.999 6、OXC 0.999 8）,定量下限分别可达到2.0、2.0、3.0 μg·mL^-1;各组分的日内、日间精密度RSD均小于4%,各方法平均回收率均大于96%,LEV、OXC、MHD低、中、高3个浓度的提取回收率均>85%,稳定性的RSD均<15%。结论：该方法操作简便、快捷,专属性强,结果准确可靠,可用于左乙拉西坦、奥卡西平及其代谢产物单羟基卡马西平的临床血药浓度监测。     

高效液相色谱法同时测定人血浆中卡马西平、奥卡西平及其活性代谢产物的浓度和临床应用

目的：建立同时测定人血浆中卡马西平（CBZ）、10,11-环氧卡马西平（CBZE）、奥卡西平（OXC）和单羟基卡马西平（MHD）浓度的高效液相色谱法,并将其应用于临床中卡马西平、奥卡西平及其活性代谢产物血药浓度的测定。方法：以苯巴比妥为内标,血浆经乙醚-二氯甲烷（2∶1）提取。色谱柱为WondaSil C₁₈柱（150 mm×4.6 mm,5 μm）,流动相为甲醇∶水=50∶50,柱温30℃,流速1.0 mL·min^-1,检测波长215 nm,进样量20 μL。结果：卡马西平、10,11－环氧卡马西平、奥卡西平和单羟基卡马西平标准曲线范围分别为0.1~20,0.05~10,0.05~20,0.2~50 mg·L^-1,最低检测限分别为0.1,0.05,0.05,0.2 mg·L^-1,日内、日间精密度均小于10%。结论：该方法灵敏准确,简便快速,适用于卡马西平、奥卡西平及其代谢产物血药浓度检测。     

HPLC法测定奥卡西平及其制剂中有关物质

目的:建立使用C₁₈色谱柱同时测定奥卡西平及其制剂中8个杂质的高效液相色谱法。方法:采用ACE Excel C₁₈(4.6 mm×150 mm, 3μm)色谱柱,流速1.0 mL·min^-1,以6.8 g·L^-1磷酸二氢钾溶液(每1 000 mL加三乙胺2 mL,用磷酸调pH 6.0)为流动相A,乙腈-甲醇(11∶8)为流动相B,梯度洗脱,检测波长240 nm,柱温45℃。结果:奥卡西平与8个杂质分离度良好,奥卡西平和卡马西平分别在0.05～4.0μg·mL^-1和0.08～40μg·mL^-1浓度范围内呈现良好线性(r≥0.999 9),奥卡西平和卡马西平的定量限分别为1.03、0.65 ng,检测限分别为0.34、0.33 ng。共测定奥卡西平原料2个企业5批样品、奥卡西平片2个企业6批样品,其中1批原料检出杂质E,含量为0.004%;3批片剂检出卡马西平,含量分别为0.008%、0.005%、0.006%;1批片剂检出杂质C和杂质D,含量为0.006%、...     

Oxcarbazepine

Oxcarbazepine (OXC) (Trileptal^®, Novartis) is one of the recently introduced anti-epileptic drugs (AEDs) in the US. This drug has demonstrated efficacy as adjunctive therapy in adults and children, and as monotherapy in adults for the treatment of seizures of partial onset. There is also convincing evidence of its efficacy in patients with newly diagnosed and refractory trigeminal neuralgia. In addition, the initial efficacy results of oxcarbazepine in other neuropathic pain conditions and in bipolar disorders are encouraging. In this review, recommendations on the optimal clinical use of OXC are given based on its pharmacokinetic profile, efficacy and tolerability in those various conditions.     

Anticonvulsant Efficacy in Sturge-Weber Syndrome

ObjectiveWe analyzed individuals with epilepsy due to Sturge-Weber syndrome to determine which anticonvulsants provided optimal seizure control and which resulted in the fewest side effects.MethodsOne-hundred-eight records from a single center were retrospectively analyzed for Sturge-Weber syndrome brain involvement, epilepsy, Sturge-Weber syndrome neuroscores, and currently used anticonvulsants.ResultsOf the fourteen anticonvulsants that had been employed, the most often used agents were oxcarbazepine or carbamazepine, and levetiracetam. Individuals whose seizures at the most recent visit were fully controlled (seizure-free) for 6 months or longer were more likely to have ever tried, or currently used, oxcarbazepine or carbamazepine than those with uncontrolled seizures. Thirty-nine of 69 individuals (56.5%) were seizure-free with oxcarbazepine or carbamazepine history versus 11 of 35 individuals (31.4%) who had not taken these agents (P < 0.05); 38 of 62 patients (61.3%) were seizure-free while currently taking these anticonvulsants versus 12 of 42 (28.6%) not taking them (P < 0.01). Patients with seizure control for 6 months or longer were less likely to have ever tried, or to currently be taking, levetiracetam than those without control. Sixteen of 56 individuals (28.6%) were seizure-free with levetiracetam history versus 34 of 48 (70.8%) without it (P < 0.001); 14 of 43 individuals (32.6%) were seizure-free and currently taking levetiracetam versus 36 of 61 (59.0%) not taking it (P < 0.01). When topiramate was added as second-line medication, five of nine patients (55.6%) experienced decreased seizure severity, and worsening of glaucoma was not reported.ConclusionsCarbamazepine and oxcarbazepine were associated with better seizure control than levetiracetam in this Sturge-Weber syndrome cohort and so may be preferred as the initial therapy. When used as adjunctive therapy, topiramate was effective in this limited analysis without a clear increased incidence of glaucoma.     

奥卡西平对戊四氮致癫(癎)幼鼠海马胶质纤维酸性蛋白表达的影响

目的 探讨奥卡西平(OXC)对慢性癫(癎)幼鼠海马星形胶质细胞表达胶质纤维酸性蛋白(GFAP)的影响.方法 50只21日龄SD幼年雄性大鼠,随机分为5组:A组(阴性对照组)、B组(阳性对照组)、C组(OXC低剂量组)、D组(OXC中剂量组)、E组(OXC高剂量组),每组10只.A组每日腹腔注射等量9g·L-1盐水;B组腹腔注射戊四氮(PTZ)40 mg·kg-1·d-1;C～E组腹腔注射PTZ 40 mg·kg-1·d-1后分别予OXC 100 mg·kg-1、OXC 200 mg·kg-1、OXC 300 mg·kg-1灌胃.连续用药21 d,观察幼鼠体质量、行为学表现;采用免疫组织化学方法检测幼鼠海马GFAP阳性星形胶质细胞的表达;应用实时荧光定量PCR方法检测幼鼠海马组织中GFAP mRNA表达.结果 与A组相比,其他各组幼鼠均有癫(癎)发作,海马组织中均发现GFAP阳性细胞数量增多(P＜0.01),GFAP mRNA的表达增加(P＜0.01);与B组相比,C～E组幼鼠癫(癎)发作潜伏时间延长,发作级别低,点燃率低(Pa＜0.05),GFAP阳性细胞数量逐渐减少(P＜0.05),GFAP mRNA表达降低(P＜0.05);与其他各组相比,E组幼鼠体质量增长缓慢(P＜0.05).结论 OXC对PTZ点燃的慢性癫(癎)引起的脑损伤有保护作用,其程度与剂量有关,但大剂量OXC会抑制幼鼠生长;OXC的这种神经保护作用可能是通过抑制星形胶质细胞表达GFAP实现的.