Therapeutic drug monitoring-based dosing of TNF inhibitors in inflammatory bowel disease: the way forward?

ABSTRACT

Introduction: Secondary loss of response to anti-tumor necrosis factor (TNF) therapy remains a challenge in the clinical management of inflammatory bowel disease (IBD) patients. A frequently observed reason for secondary loss of response to TNF blockers is inadequate drug exposure and sub-therapeutic serum drug concentrations.

Areas covered: This review presents an overview of recent research on therapeutic drug monitoring (TDM)-based dosing with anti-TNF agents in IBD. The role of reactive and proactive TDM and different approaches on how to optimize anti-TNF treatment are discussed.

Expert opinion: Due to variations within and between patients, the ‘one size fits all’ theory does not apply to all IBD patients receiving anti-TNF agents. Timing of TDM (i.e. reactive versus proactive) is a matter of debate. Both strategies might optimize anti-TNF treatment, although most trials did not show a clinical benefit compared to conventional dosing up to now. So-called dashboard systems might have an additive value in the optimization of anti-TNF treatment, since these tools enable clinicians to really personalize anti-TNF treatment.     

高效液相色谱法测定苯妥英钠的血药浓度

目的 建立HPLC测定血清中苯妥英钠浓度的方法.方法 采用高效液相色谱法,色谱柱为C<,18>柱(4.6mm×150mm,5μm),柱温:30℃,检测波长:220nm,流动相为甲醇-乙腈-水(10:30:60),流速为1mL·min<'-1>.结果 在5～40μg·mL<'-1>范围内线性良好,R=0.9993172,...     

Effect of green tea on pharmacokinetics of 5-fluorouracil in rats and pharmacodynamics in human cell lines in vitro

Tea drinking is widely practiced in the world and has recently increased among cancer patients. However, the effects of concurrent consumption of tea on the bioavailability and the net therapeutic potential of co-administered chemical drugs are not clear. In this study, the effects of green tea on the pharmacokinetics of 5-fluorouracil (5-FU) in rats and the pharmacodynamics in human cell lines in vitro were studied. The pharmacokinetic experiment indicated that there was an approximately 151% increase in the maximum plasma concentration (C_max) and an approximately 425% increase in the area under the plasma concentration curve (AUC) of 5-FU in the green tea-treated group compared with the control group. Green tea consumption increased the plasma concentration of 5-FU. In addition, the pharmacodynamics experiment showed that at the moderate dose level (equivalent to <6 cups daily in human), neither fresh green tea extract nor (−)-epigallocatechin-3-gallate (EGCG) showed significant additive effects on the cytotoxicity of 5-FU in human cell lines. The results showed that it is crucial to perform therapeutic drug monitoring (TDM) when the cancer patients have a habit of drinking green tea.     

亚胺培南血药浓度测定方法改进及其在血浆中稳定性考察

目的:建立高效液相色谱法测定人血浆中亚胺培南浓度,并重点考察亚胺培南血浆样品的稳定性。方法:采用Venusil XBP C₁₈ (5μm,4.6mm×250 mm)色谱柱,以10 mmol·L^-1磷酸二氢钾-含四丁基溴化铵(0.3 mmol·L^-1)甲醇液(96:4,V:V)为流动相,调节pH至7.2,柱温为30℃,内标为5-羟基吲哚-3-醋酸,检测波长300 nm。稳定剂0.5mol·L^-1 3-吗啉丙磺酸缓冲液(pH6.8)-乙二醇-水,体积比2:1:1。结果:低、中、高3个浓度提取回收率分别为(89.6±1.7)%,(93.9±2.2)%,(91.4±0.4)%,批内、批间RSD均小于15%;血浆中亚胺培南在0.1~100 μg·ml^-1浓度范围内线性关系良好(r=0.995~0.996),定量下限为0.1μg·ml^-1;不加稳定剂时,含亚胺培南的血浆样品在室温、4℃、-30℃条件下分别可以稳定2,6,8 h,加入稳定剂后分别为6,12,48 h。结论:本试验建立的分析方法线性范围宽,操作简便,准确度高,可用于亚胺培南血药浓度的测定,适用于重症感染患者治疗药物监测。     

糖尿病合并抑郁患者的健康教育

目的　探讨健康教育与心理干预对 2型糖尿病合并抑郁患者的抑郁症状及糖脂代谢的作用。方法　将 2型糖尿病合并抑郁患者 77例随机分为干预组 (n =39)与对照组 (n =38)。对照组给予常规药物治疗 ,干预组则在常规药物治疗的基础上进行 3个月的健康教育与心理干预。分别于治疗前、治疗后进行Zung抑郁自评量表、汉密顿抑郁量表评分及糖脂代谢水平检测。结果　经健康教育与心理干预 3个月后 ,干预组抑郁自评量表和汉密顿抑郁量表积分显著下降 (P <0 0 1) ,显著低于对照组 (P <0 0 1) ,抑郁指数显著降低 (P <0 0 5 ) ,糖脂代谢显著改善 (P <0 0 5 )。结论　健康教育与心理干预可改善 2型糖尿病合并抑郁患者的抑郁症状及糖脂代谢     

抗癫痫药物引起代谢性骨病的研究

本文对服用抗癫痫药物达1～1.5年的78例患儿进行了治疗药物监测(TDM)、血生化及放射学骨矿含量(BMC)等定量指标的观察研究。结果表明,BMC水平下降,碱性磷酸酶(AKP)活性与治疗呈正相关。当苯巴比妥钠(PBS),丙戊酸钠(SV)的TDM(?)值分别大于18.21mg/ml、74.25mg/ml时,AKP活性增加。     

高效液相色谱法测定血浆缬沙坦浓度

目的　建立一种高效液相色谱法以测定血浆中缬沙坦浓度。方法　色谱柱 :LichrospherC18高效液相柱 ;流动相 :0 0 1mol·L-1磷酸二氢钾缓冲液 (pH 3 1)∶乙腈 =5 3∶4 7(V/V) ,流量 1 0ml·min-1;检测器 :荧光检测 ,激发波长2 6 5nm ,发射波长 378nm。血浆样品经盐酸酸化 ,乙酸乙酯萃取 ,分离有机相 ,氮气吹干 ,流动相溶解后进样。结果　缬沙坦保留时间为 12 5min ,分离良好 ;标准曲线在 5 9～2 36 0 μg·L-1范围内呈线性 ;日间RSD为 5 94 %～ 8 4 1% ,日内RSD为 2 83%～ 7 0 7% ,回收率为 81 13%± 5 2 6 %。选择住院高血压病人 15例 ,每日口服缬沙坦胶囊 80mg ,分别于第 4、7d测定其稳态峰、谷浓度 ,谷浓度为 (16 5 99±6 0 2 2 ) μg·L-1,峰浓度为 (5 2 6 90± 337 0 6 ) μg·L-1。结论　该法灵敏、简便 ,适用于血药浓度监测及其动力学研究     

A sensitive new method for clinically monitoring cytarabine concentrations at the DNA level in leukemic cells

Cytarabine (ara-C), a major antileukemic agent, is phosphorylated in the cell to cytarabine triphosphate (ara-CTP), which is then partly incorporated into DNA. The drug incorporation into DNA poisons the extending primer against further incorporation of deoxyribonucleotides including dCTP, ultimately inhibiting DNA synthesis. While intracellular ara-CTP concentration has been found to predict clinical outcome, cytotoxicity in vitro is determined primarily by the extent of drug incorporation into DNA. However, clinically appropriate quantitation methods for ara-C at the DNA level have not been available. We developed a sensitive new method for monitoring ara-C incorporated into DNA in vivo. After DNA from leukemic cells was fractionated using the Schmidt-Thannhauser-Schneider method, it was degraded to constituent nucleosides to release ara-C, which was isolated from the nucleosides using HPLC and then measured by radioimmunoassay. Recovery for DNA fractionation, ara-C release by degradation, and ara-C isolation were 92.0+/-6.4%, 90.7+/-9.4%, and 98.5+/-1.4%, respectively. The method was found to determine ara-C incorporation into DNA of ara-C-treated HL 60 cells in vitro with minimal interassay variation. The values determined were compatible with those determined by scintillation counting in parallel experiments using tritiated ara-C. Our method could be used to monitor DNA-incorporated ara-C concentrations during ara-C therapy, together with plasma ara-C and intracellular ara-CTP concentrations. ara-C incorporation into DNA appeared to be associated with intracellular retention of ara-CTP or persistence of plasma ara-C. Thus, the present method is sensitive, accurate, precise, and may permit therapeutic drug monitoring at the DNA level for better individualization of antileukemic regimens.