卡马西平血浓度监测及苯妥英钠对其血浓度的影响

46例癫痫患者,30例单用卡马西平(CBZ)治疗,16例CBZ 合用苯妥英钠(PHT)、服药剂量与血药浓度呈正相关。CBZ 的血药浓度与抗癫痫作用之间存在着较大的个体差异,本组资料提示CBZ 血药浓度以6～12μg/ml 为宜。加用PHT0.2±0.1/d,CBZ 的血浓度显著下降。     

癫痫患者和非癫痫患者苯妥英钠中毒

目的 探讨癫痫和非癫痫患者苯妥英钠(PHT）中毒的临床表现、诊断及治疗异同点,并复习PHT中毒的新进展。方法 回顾性分析我院1988-2008年14例癫痫和非癫痫住院患者PHT中毒的临床表现、中毒的原因、用药情况、PHT血药浓度及预后。 结果 两组患者临床皆表现为小脑性共济失调,部分患者有锥体外系和锥体束表现。癫痫患者用药史明确,诊治及时;而3例非癫痫患者皆因不知情用药所致,3例患者因哮喘服用肺宝,医患忽略其PHT成分,拖延诊断达2年左右;其临床表现为发作性共济失调,发作频率与间隔和哮喘发作相一致。PHT中毒预后良好,停药后症状消失。结论 首次报道PHT复方制剂用于治疗哮喘造成中毒3例。因此,凡遇病因不明小脑综合征患者应高度怀疑PHT中毒的可能。PHT不宜作为一线药物用于非癫痫疾患,并对PHT易中毒的药代动力学和中毒的内因和外因进行文献复习。     

丙戌酸钠血药浓度监测临床分析

目的:探讨分析丙戌酸钠血药浓度监测临床应用。方法:2004年1月～2008年10月我院门诊或住院收治的癫痫患者218例。对服用VPA达治疗剂量后3个月患者进行血药浓度测定及疗效评定。结果:血药浓度<50μg/mL33例(15.13%),50μg/mL～100μg/mL156例(71.55%),>100μg/mL29例(13.3%)。结论:临床治疗药物监测中,不能凭剂量来估计血药浓度和评价疗效,应进行VPA的血药浓度监测,并结合患者具体情况进行综合分析,及时调整剂量,实施个体化给药,确保用药安全有效。     

我院2009年抗癫痫药物血药浓度监测结果分析

目的:促进临床合理应用抗癫痫药物并提高其疗效。方法:回顾性分析我院2009年门诊或住院患者服用丙戊酸(VPA)、卡马西平(CBZ)、苯妥英钠(PHT)的487例癫痫患者的血药浓度监测结果。结果:487例监测中,248例(50.92%)在有效血药浓度范围内;177例(36.34%)低于有效血药浓度;51例(10.47%)高于有效血药浓度;11例(2.26%)未检出血药浓度。其中,在有效血药浓度范围内的3种药物比例分别是VPA(48.18%)、CBZ(74.29%)、PHT(10.87%)。结论:抗癫痫药物的血药浓度监测为临床设计个体化给药方案提供了依据,是保证安全、有效用药的重要措施。     

卡巴咪嗪与苯妥英相互作用的双重效 应

对于某些癫痫患者,血浆苯妥英(PHT)浓度随卡巴咪嗪(Carbamazepine,CBZ)的给予而增高。当PHT浓度接近治疗范围上限时,给予CBZ很易导致PHT的毒性临床表现。显然CBZ可能降低PHT的代谢,使PHT在血浆中蓄积。本试验选择A组32例患者,给予CBZ剂量逐渐增加,PHT剂量不变(每日5.29±1.24 mg/kg);B组22例患者,给予PHT剂量逐渐减少,CBZ剂量不变(每日19.17±     

维吾尔族癫痫患儿奥卡西平活性代谢产物血药浓度监测分析

目的:探讨维吾尔族癫痫患儿奥卡西平(OXC)活性代谢产物10-羟基卡马西平(MHD)血药浓度与年龄、性别及给药剂量的相关性。方法:建立高效液相色谱法(HPLC)测定79例维吾尔族癫痫患儿MHD的稳态血药浓度,记录患儿年龄、性别及给药剂量等详细信息,利用SPSS 17.0软件进行数据分析。结果:服用8~46 mg·kg^-1·d^-1的奥卡西平后,不同年龄组患儿MHD的稳态血药浓度随着年龄的增加有所升高,但是差异没有统计学意义(P>0.05);相同条件下,不同性别组患儿MHD的稳态血药浓度差异没有统计学意义(P>0.05)。结论:在每千克体质量给药剂量无差异的情况下,维吾尔族癫痫患儿MHD的血药浓度虽随年龄增加而升高,但差异无统计学意义,且与性别无相关性。因此选用奥卡西平治疗癫痫时应定期监测MHD血药浓度并及时调整剂量,为维吾尔族癫痫患儿制订个体化给药方案提供基础,以避免不良反应的发生。     

抗癫痫药物中毒病例的血药浓度监测及分析

目的：分析分别服用4种抗癫痫药物苯妥英（PHT）、苯巴比妥（PB）、卡马西平（CBZ）、丙戊酸（VPA）中毒病例的血药浓度及其中毒原因，特点，方法：对942例癫痫患者所服抗癫痫药采用荧光偏振免疫法（FPIA）进行血药浓度监测，对高于有效血药浓度范围的106例患者进行分析。结果：中毒病例的血药浓度有较大的个体差异，部分病例在服用常规治疗剂量情况下，血药浓度就已高于有效范围，并出现中毒症状，单一用药时PHT的中毒发生率明显高于其余3种药物（P＜0．01）。联合用药中苯妥英钠与卡马西平联用的中毒比较较高。结论：适时监测血药浓度可避免抗癫痫药物中毒。     

1 018 例癫痫患儿丙戊酸钠血药浓度监测及影响因素分析

目的:分析癫痫患儿丙戊酸钠(VPA)血药浓度的监测结果,为临床用药提供依据。方法:采用高效液相色谱法测定1 018例癫痫患儿的VPA血药浓度,分析年龄、性别、给药剂量和药物剂型等因素对VPA血药浓度的影响以及VPA血药浓度与疗效之间的关系。结果:癫痫患儿VPA血药浓度低于治疗窗的528例(51.9%),位于治疗窗内的464例(45.6%),高于治疗窗的26例(2.6%)。年龄、性别和给药剂量对VPA血药浓度的影响差异有统计学意义(P < 0郾05),药物剂型对VPA 血药浓度的影响差异无统计学意义(P>0.05),VPA血药浓度与疗效之间存在统计学差异(P<0.05)。结论:VPA血药浓度个体差异大,且受癫痫患儿年龄、性别和给药剂量等因素影响,为实现个体化药物治疗,应常规监测血药浓度。     

血液中游离苯妥英钠的测定方法及其临床价值

苯妥英钠(Phenytoin sodium,PHT)是一种有效的抗癫痫药物,临术上主要用于癫痫大发作和精神运动性发作的防治。由于有效治疗浓度范围窄(10～20mg/L),且用药剂量与药理作用强度间的关系存在很大的个体差异[1]。据报道,应用血药浓度监测技术可使癫痫发作完全控制率由50%提高至80%[     

苯妥英钠血药浓度监测与个体差异

目的:通过对苯妥英钠血药浓度监测结果的分析,探讨苯妥英钠剂量与患者血药浓度以及临床疗效间的相互关系.方法:采用化学发光免疫分析法,对98例服用苯妥英钠的癫痫患者的血药浓度监测结果及临床疗效进行分析与评价.结果:苯妥英钠的有效剂量和中毒剂量与分别对应的血药浓度的个体差异均较大.结论:苯妥英钠治疗癫痫患者应重视血药浓度的监测,并应结合临床,着眼于个体化给药.     

Phenytoin concentration in head hair sections: a method to evaluate the history of drug use

Phenytoin (PHT) levels were determined in sections of head hair taken from 60 patients (34 males and 26 females), aged 5 to 69 years, who were regularly receiving the drug. The hair sectional analysis included dissolution, liquid phase extraction procedures, and immunoassay (Abbott TDx) or high-pressure liquid chromatography (HPLC) analytical techniques. The values of PHT levels in the hair from the first section (close to the hair root) to the fifth section for female patients were 18.0, 15.2, 13.1, 11.6, and 10.7 microg/g, respectively, according to HPLC measurements. There were no significantly different results obtained using the immunoassay technique, according to which the mean values of PHT in the hair sections were 17.9, 15.2, 13.1, 11.9, and 10.9 microg/g, respectively, from the first to the fifth sections. The corresponding mean values for male patients by HPLC and immunoassay techniques, respectively, were 17.9, 15.0, 12.5, 12.1, and 12.3 microg/g and 17.8, 14.9, 12.2, 11.9, and 121 microg/g. Generally, a reduction of drug concentrations in hair from the first to the subsequent segments was observed. The hair PHT concentrations were found to be dependent on the dosage (by fluorescence polarization immunoassay: r = 0.987, p < or = 0.02; by HPLC: r = 0.988, p < or = 0.02). Mean dose and assay outcome values by hair color and correlation between hair PHT mean values, daily mean doses of the drug, and patients' age are presented. The differences among doses according to hair color were significant. PHT hair profiles from female and male patients compared with the mean +/- SD concentrations of the hair sections are discussed. The data indicate the possible use of hair section testing as a marker of the dosage history and the compliance of patients receiving long-term treatment with PHT.     

一线抗癫癎药物血药浓度监测结果分析

目的:对一线抗癫癎药物血药浓度监测结果进行回顾性分析,指导临床合理用药。方法:对801例服用一线抗癫癎药物病人的血药浓度进行分类汇总,并对结果进行统计学分析。结果:各药在有效血药浓度范围内的病例百分率差异显著(P<0.01),分别为丙戊酸钠(VPA)75.2%、苯巴比妥(PB)67.3%、卡马西平(CBZ)53.1%、苯妥英钠(PHT)20.8%。VPA使用率最高,为60.5%,其血药浓度存在性别差异(P<0.01)。CBZ血药浓度存在年龄差异(P<0.01)。多药联用血药浓度升高的病例增加(P<0.01),以PHT/CBZ方案最为突出。CBZ/VPA、PB/VPA方案在控制率、安全性方面比较好。结论:血药浓度监测对癫癎治疗具有极其重要的临床意义。     

癫痫患者2种治疗药物浓度的监测及其临床意义

目的：监测治疗癫痫患者血清中苯妥英（ＰＨＴ）和卡马西平（ＣＢＺ）的浓度。方法：建立高效液相色谱法,测定住院和门诊７８例癫痫患者血药浓度。结果：其中服用苯妥英２３例,卡马西平５５例,低于治疗有效浓度分别有１４例和１９例,各占６０．８７％和３４．５５％,中毒浓度１例。结论：癫痫患者的治疗与苯妥英和卡马西平的用药水平有关,治疗剂量不能仅凭经验用药,有条件则应进行血药浓度监测,实行个体化给药。     

左旋氧氟沙星对苯妥英钠在家兔的药代动力学影响的研究

目的 :研究左旋氧氟沙星对苯妥英钠血药浓度及药代动力学参数的影响。方法 :应用紫外分光光度法测定家兔喂服左旋氧氟沙星前及10d后单剂量静脉注射苯妥英钠的经 -时血药浓度 ,以“3p87”药代动力学程序拟合药动学参数。结果 :苯妥英钠经 -时血药曲线符合二室开放模型 ,合用左旋氧氟沙星后 ,苯妥英钠血药浓度均有不同程度的降低 ,部分药代动力学参数也有明显的改变。结论 :提示两药合用使苯妥英钠代谢明显加快     

Vigabatrin-induced decrease in serum phenytoin concentration does not involve a change in phenytoin bioavailability

The possibility that vigabatrin (VGB) decreases serum phenytoin (PHT) concentration by lowering the oral bioavailability of PHT was investigated in 21 patients with epilepsy. Each patient was switched from oral to intravenous PHT for 5 days before and after combined treatment with VGB. After VGB (2-3.5 g day(-1) for at least 5 weeks), serum PHT concentrations decreased slightly from 87 +/- 25 to 76 +/- 31 micromol l(-1) (means +/- s.d., P < 0.05), but in a subgroup of seven patients the decrease was more prominent (from 72 +/- 22 to 49 +/- 17 micromol l(-1), P < 0.005). At baseline (before VGB), serum PHT remained unaffected (85 +/- 30 micromol l(-1)) after switching PHT dosage to the intravenous route, indicating that the oral availability of the drug was virtually complete. During VGB treatment, serum PHT was also unchanged (74 +/- 34 micromol l(-1)) after switching from oral to intravenous therapy, and this was also true for the subgroup of patients showing a prominent interaction (48 +/- 18 micromol l(-1)). The urinary recoveries of PHT and its metabolites pHPPH and mHPPH remained constant throughout the study. It is concluded that the oral availability of PHT is unaffected by VGB and that the VBG-induced decrease in serum PHT is mediated by alternative mechanisms.     

Population estimation of valproic acid clearance in adult patients using routine clinical pharmacokinetic data

The aim of the present study was to estimate valproic acid (VPA) clearance values for adult patients with epilepsy, using serum concentrations gathered during their routine clinical care. Retrospective steady state serum concentrations data (n=534) collected from 208 adult patients receiving VPA were studied. Data were analysed according to a one-compartment model using the NONMEM program. The influence of VPA daily dose (Dose), gender, age, total body weight (TBW), and comedication with carbamazepine (CBZ), phenytoin (PHT) and phenobarbital (PB) were investigated. The results of the population pharmacokinetics analysis were validated in a group of 30 epileptic patients. The final regression model for VPA clearance (Cl) was: $?rm Cl?left (?rm L/h ?right )=0?rm. 004?times TBW?times Dose ?0.304??rm ?times 1.363?,?rm CBZ?times 1. 541?,?rm PHT?times 1.397?,?rm PB.$ The inter-individual variability in VPA clearance, described by a proportional error model, had a variation coefficient (CV) of 23.4% and the residual variability, described using an additive model, was 11.4 mg/L. These results show that VPA clearance increased linearly with TBW, but increases nonlinearly with increasing VPA daily dose. Concomitant administration of CBZ, PHT and PB led to a significant increase in VPA clearance. The model predictions in the validation group were found to have satisfactory precision and bias. In conclusion, inter-individual variability in VPA clearance can be partly explained by TBW, daily dose and bitherapy with CBZ, DPH or PB. Inclusion of these factors allows this variability to be reduced by 37.23% which may be very useful for clinicians when establishing the initial VPA dosage regimen. However, the magnitude of inter-individual plus residual variabilities, remaining in the final model, render these dosage predictions imprecise and justify the need for VPA serum level monitoring in order to individualize dosage regimens more accurately.     

Clinical utility of a Bayesian dosing program for phenytoin

We performed two studies to assess the clinical utility of a Bayesian regression analysis computer program for phenytoin (PHT). In a randomized prospective study of 40 epileptic patients, the dosing program was significantly more accurate (p = 0.002) and less biased (p = 0.02) than a group of physicians at hitting a target PHT serum-concentration. Initial serum PHT concentrations that were not steady state were associated with the largest dosing errors by physicians but did not affect the accuracy of the dosing program. In a second study, we used the dosing program to predict 91 serum concentrations in 31 patients with PHT toxicity after the drug was stopped (initial concentration 26-69 micrograms/ml). The program predicted serum concentrations with a mean error of 3.49 +/- 0.29 micrograms/ml without significant tendency to over- or underpredict. We conclude that this dosing program may aid clinicians by improving dosing accuracy and predicting serum concentrations in patients with PHT toxicity.     

Dosing accuracy of antiepileptic drug regimens as determined by serum concentrations in outpatient epilepsy clinic patients

To evaluate the ability of clinicians to accurately dose antiepileptic drugs (AEDs), 2,958 serum concentrations in two outpatient epilepsy clinics were studied. Serum concentrations of phenytoin (PHT) were significantly less likely to fall within the therapeutic range (TR) when compared to carbamazepine (CBZ) or phenobarbital (p less than 0.0001) even when there was evidence that patient compliance was good. This difference remained significant when the second through fourth follow-up serum concentrations were analyzed. PHT concentrations were more likely to be below than above the TR (p less than 0.0001). CBZ concentrations were least likely of the three AEDs to be below the TR (p less than 0.01). Analysis of factors influencing AED metabolism and of data from previous studies implies that saturable metabolism and variable time to steady state for PHT are responsible for these findings. These results support the increased use of dosing aids for PHT that may help clinicians more accurately choose PHT doses and estimate time to steady state.     

Use of three probes to assess the influence of sex on hepatic drug metabolism

Clearances of phenytoin (PHT), ethosuximide, and theophylline were estimated by a single-dose, single-sample strategy in healthy, young adult men and women. PHT concentrations were measured in salivary ultrafiltrates, ethosuximide concentrations were measured in saliva, and theophylline concentrations were measured in plasma. Estimates of the clearances of these three probes of hepatic drug-metabolizing enzymes revealed a trend toward slightly lower clearances among women compared to men: mean PHT clearance 15% lower, ethosuximide clearance 27% lower, and theophylline clearance 14% lower. However, only differences in ethosuximide clearances were statistically significant. The use of oral contraceptive steroid (OCS) drugs on PHT and ethosuximide clearance was examined, and no significant effects were detected.