Measuring the appropriateness of carbamazepine and valproic acid prescribing and utilization using a newly implemented online system in the Tabuk Region of Saudi Arabia

Epilepsy is a common neurologic disorder, which is efficiently treated with carbamazepine and valproic acid. Moreover, Saudi Ministry of Health implemented a new E-system for Poison Control Centers called Awtar to enhance technology utilization in ensuring patients’ satisfaction and to improve treatment outcomes. Therefore, we conducted this study to assess appropriateness of indication of requests and therapeutic levels of carbamazepine and valproic acid in Tabuk area, North West Saudi Arabia. This is a retrospective observational study conducted in Poison Control & Forensic Chemistry Center, Tabuk, Saudi Arabia. Patients’ data were obtained for years 2018 and 2019. The blood levels of carbamazepine and valproic acid were measured by Therapeutic Drug Monitoring (TDM) Unit. We selected patients treated with either valproic acid or carbamazepine alone without any history of drug allergy. Data of 264 patients were extracted from Awtar E-system. Serum carbamazepine levels were within therapeutic range in 114 patients (75.50%), above-therapeutic range in 13 patients (8.61%) and sub-therapeutic levels in 24 patients (15.89%). Regarding serum valproic acid, it is within therapeutic range in 62 patients (54.87%), above-therapeutic range in 11 patients (9.73%) and sub-therapeutic levels in 40 patients (35.40%). In conclusion, this study gives information about partial appropriateness of usage of carbamazepine and low level of appropriateness of valproic acid. However, more efforts are needed to improve results of appropriateness of indication of antiepileptic drugs.     

苯巴比妥在患儿血清样品中的稳定性

目的:探讨患儿苯巴比妥(PB)血清样品在冷处储存的稳定性.方法:荧光偏振免疫法(FPIA)测定30例患儿应用PB治疗时的血药浓度,比较其血清样品当天测定浓度(C1)与其在冷处储存7 d后测定浓度(C7).结果:PB血药浓度C1与C7呈正相关(P＜0.01),其回归方程:C7＝1.054 5C1－1.275 8,r＝0.983 1.平均Re(C7/C1,相当于PB在患儿血清中的平均回收率)为(100.4±4.8)%,RSD为4.70%(n＝30),且两者的各组偏差［(C7－C1)/C1］均小于10%.结论:患儿血清样品在冷处储存7 d,其PB能保持稳定,有利于常规治疗药物监测(TDM)时的样品储存.     

HPLC法同时测定血清中苯巴比妥、苯妥英和卡马西平的浓度

目的 :建立快速测定血清中苯巴比妥、苯妥英和卡马西平浓度的方法。方法 :色谱柱DiamonsilC18(4 .6mm× 2 5 0mm ,5 μm) ,流动相甲醇∶水∶乙腈 (4 0∶4 5∶15 ) ,流速1.2ml·min-1,检测波长 2 4 0nm ,内标硝西泮 ,柱温 4 0℃。结果 :提取回收率为 84 .4～ 89.2 % ,日内和日间RSD均 <7.9% ;标准曲线相关性良好。对 10 4例患者作血清浓度监测 ,临床效果满意。结论 :本方法可作为苯巴比妥、苯妥英和卡马西平的血药浓度监测的常规方法。     

抗肿瘤药物的治疗监测

大多数抗肿瘤药具有治疗指数低、毒性大、药动学参数个体差异大的特性，临床需进行治疗药物监测，以达到个体化给药。但治疗药物监测最基本的条件——量效关系，对大多数肿瘤药而言只是量毒关系，基于提高临床疗效的治疗药物监测除少数药物外目前尚不可行。     

ELISA法与MEIA法快速定量检测肝移植患者乙肝免疫球蛋白滴度

目的:比较微粒子酶免疫法(MEIA)和酶联免疫法(ELISA)检测肝移植患者乙肝免疫球蛋白滴度(HBIG)的特点,总结其在II临床HBIG滴度检测中的应用.方法:分别以MEIA和ELISA平行测定50,100,500IU·L-1的HBIG标准品,比较两种方法的准确度、精密度、相关性及各自特点.结果:MEIA和ELISA方法学的回收率分别为(105.32±1.85)%和(103.71±3.76)%,RSD分别为(3.67±2.30)%和(2.75±0.74)%.检测HBIG滴度≤160IU·L-1时,两个方法的相关性为CMEIA=0.709CELISA 30.142,r=0.784 0(n=26).当HBIG滴度＞160IU·L-1时,两方法检测结果CMEIA=-0.010CELISA 159.197,r=0.032 0(n=29).结论:ELISA法可用于常规的HBIG检测,而MEIA的检测范围比较宽,不仅可用于常规HBIG的检测,更适合HBIG被动免疫后人群的临床监测.     

肝癌患者5-氟尿嘧啶血药浓度的监测与测定方法的改进

目的:本文用改进的高效液相色谱(HPLC)法测定8位肝癌患者静脉滴注750 mg 5-Fu后7个时间点的血药浓度.方法:采用HPLC-紫外检测(标准曲线法).提取:改用乙腈加异丙醇;流动相:甲醇∶乙腈∶水(25∶5∶70),内加四丁基溴化铵,检测波长265 nm.结果:分离良好,完全无血杂质干扰;回收率高(>91%),日内精密度、日间精密度<6%,监测结果血浓个体差异极大(2.5倍以上).结论:本法取血量少,提取方法简单,离子对试剂效果佳,分离良好,灵敏度高,线性范围宽(0.2～25.0 mg·L-1),适用于基层医院的治疗药物监测(TDM). 本实验证实,5-Fu血浓个体差异较大,应该进行TDM,以实行个体化给药方案,使用药更安全、有效、合理和经济.     

反相高效液相色谱法测定血液中去甲万古霉素浓度的研究

目的：建立去甲万古霉素血药浓度的反相高效液相色谱（RP －HPLC）测定法。方法以替硝唑或甲硝唑为内标,血液样品处理采用15％ HClO4沉淀、高速离心,NH4 Ac 溶液稀释后进样。色谱分析使用 Kromasil C18柱（150 mm ×4．6 mm,5μm）,流动相组成为甲醇—乙腈—40 mmol·L －1 KH2 PO4缓冲液（含0．1％磷酸）＝15∶5∶80（v／v）,进样量为20μL,流速为1．0 mL· min －1,柱温35℃,紫外检测波长236 nm。灵敏度 AUFs ＝0．02,以峰面积、内标法定量。结果该法在去甲万古霉素浓度（X）为5．0～160 mg·L －1间呈良好线性关系,相关系数 r ＝0．9985（n ＝6）,血清最低检测浓度为2．5 mg·L －1（S ／N≥3）,日内、日间 RSD ＜10％,一个月内、反复冻融后的稳定性考察 RSD ＜10％。结论此法快速、简便、灵敏、可靠,适用于去甲万古霉素血药浓度监测。     

Impact of sampling time deviations on the prediction of the area under the curve using regression limited sampling strategies

The regression limited sampling strategy approach (R‐LSS), which is based on a small number of blood samples drawn at selected time points, has been used as an alternative method for the estimation of the area under the concentration–time curve (AUC). However, deviations from planned sampling times may affect the performance of R‐LSS, influencing related therapeutic decisions and outcomes. The aim of this study was to investigate the impact of different sampling time deviation (STD) scenarios on the estimation of AUC by the R‐LSS using a simulation approach. Three types of scenarios were considered going from the simplest case of fixed deviations, to random deviations and then to a more realistic case where deviations of mixed nature can occur. In addition, the sensitivity of the R‐LSS to STD in each involved sampling point was evaluated. A significant impact of STD on the performance of R‐LSS was demonstrated. The tolerance of R‐LSS to STD was found to depend not only on the number of sampling points but more importantly on the duration of the sampling process. Sensitivity analysis showed that sampling points at which rapid concentration changes occur were relatively more critical for AUC prediction by R‐LSS. As a practical approach, nomograms were proposed, where the expected predictive performance of R‐LSS was provided as a function of STD information. The investigation of STD impact on the predictive performance of R‐LSS is a critical element and should be routinely performed to guide R‐LSS selection and use. Copyright © 2015 John Wiley & Sons, Ltd.     

临床药师参与1例车祸致重症感染患者临床治疗万古霉素谷浓度不达标的原因分析

目的:分析车祸致重症感染患者万古霉素谷浓度不达标的原因,探究临床药师的药学监护过程。方法:临床药师参与万古霉素给药方案的制订,对重症感染患者开展治疗药物监测(TDM)和药学服务。结果:万古霉素的血药浓度受患者体质量、年龄、肾功能、体液量及表观分布容积等多种因素的影响。结论:万古霉素的个体差异较大,影响因素较多,临床医生和药师应对万古霉素TDM,关注其谷浓度的变化。