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。     

癫痫患者血浆丙戊酸钠稳态谷浓度影响因素分析

目的:探讨癫痫患者口服丙戊酸钠(VPA)稳态谷浓度与体内病理生理因素以及联合用药的相关性,为临床合理使用VPA提供参考依据。方法:采用回顾性调查方法在空军总医院收集30例因癫痫口服VPA的患者病历资料,记录患者性别、年龄、VPA单位体重剂量、血药浓度及相应生化检验值。应用SAS软件(6.04版)对数据进行多元线性回归分析。结果:VPA稳态谷浓度与血清白蛋白(ALB)、单位体重剂量(mg.kg-1)具有显著正相关性(P<0.05);与肝药酶诱导剂具有显著负相关性(P<0.05)。结论:临床使用VPA时应重点考虑ALB、单位体重剂量和肝药酶诱导剂对VPA血药浓度的影响,定期监测其血药浓度。     

不同剂型对儿童丙戊酸血药浓度的影响

目的研究剂型因素对丙戊酸血药浓度的影响,为丙戊酸钠临床个体化给药提供理论依据。方法收集2018年11月1日至2019年6月30日于首都医科大学宣武医院儿科进行丙戊酸钠血药浓度监测的患者信息,分析丙戊酸钠剂型对丙戊酸血药浓度的影响。结果我院癫痫患儿丙戊酸钠平均血药浓度为(67.71±18.03)μg/ml,血药浓度达标率为80.56%。二元Logistic回归分析结果表明,日剂量和剂型对丙戊酸钠血药浓度有显著影响(P<0.05)。相比单用口服液和单用缓释片而言,丙戊酸钠缓释片和口服液联合使用的方式能够维持更高的血药浓度,患儿癫痫发作控制情况更好,差异均有统计学意义(P<0.05)。结论丙戊酸剂型对丙戊酸血药浓度存在明显的影响。临床药师应发挥专业优势,重视药物剂型的选择,为临床抗癫痫药物合理应用提供指导。     

丙戊酸钠血药浓度监测结果分析

目的：对丙戊酸钠血药浓度监测结果影响因素进行分析,为临床合理用药提供参考。方法：采用回顾性分析方法,收集某三甲医院2017年1-11月85例丙戊酸钠血药浓度监测结果,采用SPSS 20.0统计软件分析血药浓度分布及性别、年龄、剂型、合并用药等因素对丙戊酸钠血药浓度的影响。结果：血药浓度小于50 μg·mL-142例（49.41%）,在有效药物浓度范围（50~100 μg·mL-1）为41例（48.24%）,结果大于100 μg·mL-1 2例（2.35%）。本次调研中患者性别、年龄、丙戊酸钠剂型及合并用药对血药浓度的影响均无统计学意义,患者日剂量与血药浓度表现出个体差异,但无剂量和血药浓度相关性。结论：患者体内丙戊酸钠血药浓度存在个体差异,在应用丙戊酸钠进行治疗时,应根据患者临床表现、血药浓度监测结果及时调整剂量,实施个体化给药, 提高药物疗效, 确保临床用药安全。     

影响住院患者丙戊酸钠血药浓度达标因素的回顾性研究

目的：探讨丙戊酸钠的血药浓度与性别、年龄、剂量、剂型、肝肾功能、合用药物等各因素的关系,为调整给药方案提出参考。方法：选取某院2016年1-12月住院期间检测丙戊酸钠血药谷浓度的患者,记录其丙戊酸钠同一剂量满3 d的第一次血药浓度数据,以及在此期间丙戊酸钠的剂量、剂型和患者的性别、年龄、合并用药（肝药酶诱导剂、抑制剂及碳青霉烯类药物）、肝肾功能等信息。规定稳态时的血药浓度在50~100 mg·L^-1范围列为达标,利用SPSS软件对数据进行卡方检验或费舍尔精确检验统计单因素影响下的达标率差异。不达标的风险因素分析采用多因素logistic回归模型。P<0.05为差异有统计学意义。结果：该院住院患者丙戊酸钠血药浓度分布大致呈现负偏态分布,且平均值低于达标浓度。非缓释剂组血药浓度达标率（31.67%）低于缓释剂组（51.85%）;低剂量组（22.86%）和中间剂量组（45.68%）血药浓度达标率低于高剂量组（64.0%）;合用酶诱导剂组血药浓度达标率（20.83%）低于没有合用者（47.86%）;合用碳青霉烯类药物者血药浓度达标率（5.56%）低于没有合用者（48.78%）,且具有统计学差异。低剂量、中等剂量、非缓释剂型、合用碳青霉烯类药和合用酶诱导剂是住院患者丙戊酸钠血药浓度低于达标浓度的独立风险因素。结论：住院患者丙戊酸钠血药浓度低于达标浓度情况较多,临床药师应根据各个独立风险因素给出剂量调整的建议以及预防措施。     

癫痫患儿丙戊酸钠血药浓度监测结果回顾分析

目的探讨癫痫患儿丙戊酸钠血药浓度与临床疗效、给药剂量、药物剂型、性别、年龄和体质量的相关性。方法回顾性查阅我院临床药学室337例癫痫患儿丙戊酸钠血药浓度监测记录,将浓度值、性别、年龄等资料录入数据库,利用SPSS 13.0软件进行分析处理。结果癫痫患儿丙戊酸钠血药浓度值与性别不存在明显的相关性,但与临床疗效、给药剂量、药物剂型、年龄和体质量密切相关。结论丙戊酸钠在患儿体内的代谢过程存在一定的个体差异性,应根据每位患儿自身的具体情况并结合血药浓度监测结果来制订个体化给药方案。     

儿童癫痫患者中丙戊酸血药浓度监测的意义及影响因素分析

目的研究丙戊酸在儿童癫痫患者中的血药浓度监测的意义和临床疗效的影响因素,旨在帮助儿童患者获得有效的血药浓度和满意的临床有效率提供依据。方法选取2019年6月—2020年3月监测丙戊酸血药浓度的106例15岁及以下的癫痫患者,对其血药浓度监测结果进行分析,并对性别、年龄、每日单位体质量给药剂量、剂型和联合用药等因素对血药浓度和临床疗效的影响进行统计学分析。结果给药剂量与血药浓度之间存在正相关性(P<0.01)。年龄和药物剂型对血药浓度的影响具有统计学意义(P<0.05);患儿年龄(3~6岁组和7~15岁组)、血药浓度、每日单位体质量给药剂量、服用丙戊酸钠缓释片等对临床疗效的影响有统计学意义(P<0.05)。结论丙戊酸血药浓度监测是评估和预测临床疗效的重要指标;血药浓度影响因素复杂,给药剂量与丙戊酸血药浓度存在显著的正相关性,年龄和药物剂型对丙戊酸血药浓度的影响具有临床意义;年龄≥3岁、血药浓度、给药剂量和服用丙戊酸缓释片是药物临床疗效的独立影响因素。     

卒中后癫痫患者丙戊酸钠血药浓度分布情况分析

目的 分析卒中后癫痫患者临床资料差异及丙戊酸钠血药浓度分布情况,为指导卒中后癫痫患者个体化用药提供依据。方法回顾性收集2020年1月～12月在徐州某三甲医院接受丙戊酸钠治疗的78例卒中后癫痫患者的临床资料,统计分析患者的血药浓度分布情况及不同因素对患者血药浓度的影响。结果 78例卒中后癫痫患者共进行117例次血药浓度监测,66例次（56.1%）在有效浓度范围内,单因素分析显示,年龄、卒中类型、药物剂型、用药剂量及合并使用碳青霉烯类药物对丙戊酸钠血药浓度的影响差异有统计学意义（P <0.05）,而性别、合并使用其他抗癫痫药物对丙戊酸钠血药浓度的影响差异无统计学意义（P> 0.05）。结论 卒中后癫痫患者丙戊酸钠血药浓度达标率偏低,用药方案要考虑卒中类型、年龄、药物剂型、用药剂量及合并用药对丙戊酸钠血药浓度的影响,治疗过程中应加强血药浓度监测并结合患者的具体情况制定用药方案。     

丙戊酸钠治疗不同年龄段癫痫患儿的疗效及血药浓度监测分析

目的 探究丙戊酸钠治疗不同年龄段癫痫患儿的疗效及血药浓度监测效果。方法 选择90例癫痫患儿作为试验对象，所有患儿均接受丙戊酸钠治疗，并进行丙戊酸钠的血药浓度监测，分析不同年龄段患儿丙戊酸钠血药浓度分布情况，并评估不同丙戊酸钠血药浓度患儿的治疗效果。结果 结果显示，<3岁年龄段患儿丙戊酸钠的血药浓度<50μg/mL的占比与其他两组年龄段患儿相比明显升高（P<0.05）；丙戊酸钠血药浓度（50～100μg/mL）占比中，3～5岁、6～12岁年龄段患儿明显高于<3岁年龄段患儿（P<0.05）。其中血药浓度>100μg/mL的中毒率高于其他两组（P<0.05），血药浓度<50μg/mL的治疗总有效率明显低于其他两组（P<0.05）。结论 不同年龄段癫痫患儿接受丙戊酸钠治疗后，其血药浓度水平存在明显差异，而对于不同丙戊酸钠血药浓度患儿而言，其治疗效果也存在较大差异，故临床需结合患儿具体情况调整用药方案，并及时开展血药浓度监测，以提高丙戊酸钠治疗效果。     

葡萄糖醛酸转移酶UGT2B7-A268G基因多态性对癫痫儿童丙戊酸血药浓度的影响

目的：在丙戊酸（VPA）单药治疗的癫痫儿童中评估葡萄糖醛酸转移酶UGT2B7-A268G位点的遗传基因多态性对VPA血清浓度的影响。方法：本研究纳入200例癫痫患儿的丙戊酸血药浓度,测定VPA稳态血清浓度。对UGT2B7编码区的A268G采用聚合酶链反应（RPLF）扩增进行基因鉴定分型。根据UGT2B7基因多态性分析VPA血清药物浓度与基因多态性的关系。结果：携带变异UGT2B7-268G一个基因型或纯合基因患儿的VPA血清药物浓度显著高于携带AA基因的患儿。由于儿童个体差异较大,根据年龄、体质量调整VPA浓度后与基因多态性仍然显著关联（P<0.05）。UGT2B7-A268G的基因多态性与Hardy-Weinberg平衡一致（P>0.05）,其中UGT2B7-268A>G等位基因频率分布的是30.00%,而G突变的基因分布频率为70.00%。结论：癫痫患儿UGT2B7基因的A268G突变可能改变丙戊酸的药物代谢动力学过程,并且不受年龄、体质量等因素干扰。UGT2B7的基因多态性对儿童丙戊酸血药浓度产生影响,测定其基因型对于获得适当的丙戊酸稳态浓度和设定起始用药剂量有积极意义     

The relationship between glucuronide conjugate levels and hepatotoxicity after oral administration of valproic acid

The aim of this study was to investigate the relationship between hepatotoxicity, levels of glucuronide conjugates of valproic acid (VPA), and the toxic metabolites of VPA (4-ene VPA and 2,4-diene VPA). We also examined whether hepatotoxicity could be predicted by the urinary excretion levels of VPA and its toxic metabolites. VPA was administrated orally in rats in amounts ranging from 20 mg/kg to 500 mg/kg. Free and total (free plus glucuronide conjugated) VPA, 4-ene VPA, and 2,4-diene VPA were quantified in urine and liver using gas chromatography-mass spectrometry. Serum levels of aspartate aminotransferase, alanine aminotransferase, and α-glutathione S-transferase (α-GST) were also determined to measure the level of hepatotoxicity. The serum α-GST level increased slightly at the 20 mg/kg dose, and substantially increased at the 100 and 500 mg/kg dose; aspartate aminotransferase and alanine aminotransferase levels did not change with the administration of increasing doses of VPA. The liver concentration of free 4-ene VPA and the urinary excretion of total 4-ene VPA were the only measures that correlated with the increase in the serum α-GST level (p < 0.094 and p < 0.023 respectively). From these results, we conclude that hepatotoxicity of VPA correlates with liver concentration of 4-ene VPA and can be predicted by the urinary excretion of total 4-ene VPA.     

β-氧化代谢基因多态性与癫痫患儿丙戊酸肝毒性的相关性

目的:分析ACSM2A、CPT1A基因多态性与癫痫患儿丙戊酸(VPA)血药浓度及肝毒性之间的相关性.方法:采用聚合酶链式反应(PCR)和直接测序法检测110例服用丙戊酸单药治疗癫痫患儿外周血ACSM2A rs1133607、CPT1A rs597316基因多态性,并采用液相色谱-质谱联用技术(LC-MS)测定血清VPA...     

359例非透析患者万古霉素血药浓度监测结果分析

目的:分析万古霉素血药浓度监测数据,为临床合理用药提供参考。方法:抽取2013–2018年我院使用万古霉素并进行血药浓度监测的非透析患者信息,回顾性分析血药浓度达标情况,探讨性别、年龄、体重、肌酐清除率和万古霉素单位体重日剂量对血药浓度的影响。结果:591例次万古霉素血药浓度在10~20 mg·L^-1的占40.27%,首次监测浓度在10~20mg·L^-1的占37.88%,复杂感染和非复杂感染患者血药浓度在10~20 mg·L^-1的分别占33.69%和42.44%。性别、年龄、体重、肌酐清除率和万古霉素单位体重日剂量均影响初始血药浓度,多元线性回归显示性别、肌酐清除率及万古霉素单位体重日剂量与初始血药浓度相关(P<0.05)。结论:我院患者万古霉素血药浓度在10~20 mg·L^-1的构成比低,临床宜结合患者具体情况制定个体化给药方案并及时参考血药浓度结果进行调整。     

丙戊酸血药浓度与血浆蛋白含量的相关性分析

目的:研究影响丙戊酸(VAP)血药浓度的相关因素。方法:测定71例癫痫患者VAP血药浓度的同时检测血浆总蛋白(TP)、丙氨酸氨基转移酶(ALT)、天门冬酸氨基转移酶(AST)等相关血液指标。结果:VAP血药浓度与TP呈负相关关系(r=—0·1793);VAP>100μg/ml与VAP<100μg/ml患者的TP分别为(65·6±5·8)、(69·0±5·6)g/L(P<0·05),其余各项指标均无显著性差异(P>0·05)。结论:VAP血药浓度受血浆TP含量的影响,TP含量过低易诱发药物中毒。     

Serum concentrations of valproic acid: influence of dose and comedication

The influence of valproate (VPA) dose, VPA preparation used, comedication (phenobarbital, phenytoin, carbamazepine) and factors such as age, weight, height, and sex on the concentration of VPA in serum was investigated. Nonlinear regression analysis showed that about 63% of the variance in the VPA morning concentrations of 259 inpatients could be explained by the following variables: dose, body weight, sex, and comedication. Age, height, and kind of preparation had no important influence on the VPA concentration. The relationship between dose and concentration of VPA is nonlinear, as the concentration does not increase proportionally with the dose but increases to a lesser extent. The serum concentration of VPA is clearly lower when the drug is given in combination with phenytoin (49.5%), carbamazepine (66.2%), or phenobarbital (76.3%) than when given alone (100%).     

Does lamotrigine influence valproate concentrations?

The aim of this study is to investigate the effect of lamotrigine (LTG) on valproate (VPA) concentrations dependent on LTG dose, LTG concentration, and additional enzyme-inducing antiepileptic drugs (AED) as well. For this purpose the following patient groups were compared: VPA monotherapy, VPA + one enzyme-inducing AED, VPA + LTG, and VPA + LTG + one enzyme-inducing AED. A total of 400 serum concentrations from 372 patients were evaluated. Two or more serum samples from the same patient were considered only if the comedication had been changed. For statistical evaluation, regression analytical methods and an analysis of variance were performed. For the analysis of variance, the VPA serum concentration in relation to VPA dose:body weight (level:dose ratio, LDR) was calculated and compared for different drug combinations. The analysis of variance revealed a significant effect of enzyme-inducing comedication (as expected) and age on the VPA LDR. Patients on LTG had a slightly lower VPA LDR, but this effect was not statistically significant. In addition, nonlinear regression analysis confirmed that patients on enzyme-inducing AED (carbamazepine, phenytoin, phenobarbital, methsuximide) had significantly lower VPA concentrations. Patients on ethosuximide had slightly but not significantly lower VPA concentrations. Patients on LTG also had significantly lower VPA levels, but this effect was only minor (-7%) and most probably not of any clinical relevance. Furthermore, the regression analysis showed that the relationship between the VPA dose per body weight and the serum concentration deviates significantly from linearity. Children less than 6 years old had lower VPA levels than older children and adults on a comparable VPA dose per body weight. Gender had no significant influence on VPA serum concentration. In addition, a subgroup of 40 patients was analyzed to see whether changing the LTG dose influences VPA serum concentrations. It did not. Thus, the authors conclude that the effect of LTG on VPA concentrations is not of clinical relevance.     

Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C

The daily dose of ribavirin is currently determined based on body weight. In the present study, the authors examined factors influencing total plasma clearance (CL(total)) and the toxic level on red blood cells of ribavirin in such body weight-based dosage adjustment in Japanese chronic hepatitis C patients (13 male and 6 female). Patients received ribavirin (600 or 800 mg/d) orally, depending on their body weights, together with interferon alpha-2b (6 million units) intramuscularly. A steady-state trough plasma concentration (C(pss)) was achieved approximately 4 weeks after the initiation of treatment, but the value was scattered among patients in a range from 1100 to 4200 ng/mL. The high C(pss) of ribavirin of approximately 4000 ng/mL decreased hemoglobin concentrations to less than 8.5 g/dL. The individual CL(total), estimated by dividing dose normalized by body weight by C(pss), of ribavirin correlated significantly with the patient's creatinine clearance. In contrast, no relationship was observed with other parameters such as age, body weight, serum creatinine concentration, alanine aminotransferase (ALT) concentration, or aspartate aminotransferase (AST) concentration, though ALT and AST concentrations decreased with ribavirin treatment in most patients. These results indicate that CL(total) of ribavirin is dependent on renal function (creatinine clearance), and hemolysis is induced by high ribavirin concentrations in plasma. Dosage adjustment of ribavirin based on renal function and body weight would provide effective and safer treatment without causing hemolysis.     

奈替米星2种给药方案血药浓度的比较

目的 :研究奈替米星不同给药方案的血药浓度、临床疗效及药物毒性。方法 :将22例下呼吸道感染患者随机分为两组 ,采用TDx法测定血药浓度 ,比较各组临床疗效 ,监测肾功能、听力。结果 :日剂量相同时 ,奈替米星1次/d给药组 (QD组 )的血药峰浓度显著高于2次/d给药组 (BD组 ) (P<0.01) ;QD组血药谷浓度均低于2μg/ml ,与BD组比较显著降低 (P<0.01) ;治疗后血清肌酐水平两组间比较有显著性差异 (P<0.05)。结论 :奈替米星1次/d给药方案较2次/d给药方案能够获得更高的峰浓度及较低的谷浓度 ,进而提高临床疗效 ,减少不良反应。