目的研究乳腺癌患者化疗后,多西他赛(docetaxel,DTX)药时曲线下面积(area under curve,AUC)与血液学毒性(中性粒细胞减少)的相关性,为患者个体化给药提供理论依据。方法选择郑州大学附属肿瘤医院2016年12月—2017年7月接受AC序贯T化疗...目的研究乳腺癌患者化疗后,多西他赛(docetaxel,DTX)药时曲线下面积(area under curve,AUC)与血液学毒性(中性粒细胞减少)的相关性,为患者个体化给药提供理论依据。方法选择郑州大学附属肿瘤医院2016年12月—2017年7月接受AC序贯T化疗方案的94例乳腺癌患者,采用胶乳免疫比浊法测定患者静脉输注DTX后的血药浓度,并通过非混合效应模型软件计算多西他赛AUC。建立利用AUC预测化疗后中性粒细胞减少百分比的数学模型。结果多西他赛AUC在(0.7~3.9)mg·h/L之间,平均值为(2.34±0.7)mg·h/L,患者间AUC的变异系数(CV%)为30%。出现低级别(0~2级)及高级别(3~4)中性粒细胞减少的AUC平均值分别为2.29 mg·h/L和2.82 mg·h/L(P=0.003)。利用多西他赛AUC预测中性粒细胞减少百分比的模型为y=-1.8672x^2+25.658x-14.92,r=0.643。结论本研究建立的利用AUC预测中性粒细胞减少百分比的数学模型,为通过测定患者AUC进行多西他赛个体化的给药提供了理论依据。展开更多
盐酸金霉素广泛应用于家畜和家禽,然而,金霉素的低溶解度限制了其应用。该试验以20 mg/kg单剂量灌服盐酸金霉素和超级金霉素,采集各时间节点的血浆样品并用UPLC/MS/MS检测其血药浓度,计算各种药动学参数,评估盐酸金霉素和超级盐酸金霉...盐酸金霉素广泛应用于家畜和家禽,然而,金霉素的低溶解度限制了其应用。该试验以20 mg/kg单剂量灌服盐酸金霉素和超级金霉素,采集各时间节点的血浆样品并用UPLC/MS/MS检测其血药浓度,计算各种药动学参数,评估盐酸金霉素和超级盐酸金霉素在肉鸡体内的ADME(Absorption distribution metabolism excretion)过程。结果表明:单剂量给药后超级盐酸金霉素的峰浓度显著高于盐酸金霉素[(4.69±1.54)μg/mL vs (1.91±0.63)μg/mL],表明超级盐酸金霉素的吸收速度快于盐酸金霉素。超级盐酸金霉素的药时曲线下面积(AUC)(Area under the concentration-time curve, AUC)也大于盐酸金霉素[(14.51±3.40) hr·μg·mL^(-1)vs (6.28±2.69) hr·μg·mL^(-1)]。表明超级盐酸金霉素到达全身血液循环的量多于盐酸金霉素,有利于提高金霉素的药效。以20 mg/kg剂量连续灌服盐酸金霉素和超级盐酸金霉素7 d后,检测肌肉和肝脏中盐酸金霉素和超级盐酸金霉素的残留量接近或低于检测限,远低于食用动物肌肉中盐酸金霉素的残留限量。因此,超级盐酸金霉素提高了盐酸金霉素的生物利用度,具有广阔的应用前景和推广价值。展开更多
This study aims to save cost of sampling for estimating the area under the amlodipine plasma concentration versus time curve in 24 hours(AUC0?24 h).Limited sampling strategy(LSS) models was developed and validated by ...This study aims to save cost of sampling for estimating the area under the amlodipine plasma concentration versus time curve in 24 hours(AUC0?24 h).Limited sampling strategy(LSS) models was developed and validated by mutilple regression model within 4 or fewer amlodipine concentration values.Absolute prediction error(APE),root of mean square error(RMSE) and visual predict check were used as criterion.The results of Jackknife validation showed that fifteen(9.4%) of the 160 LSS based on regression analysis were not within an APE of 15% by using one concentration-time point.156(97.5%),159(99.4%) and 160(100%) of the 160 LSS model were capable of predicting within an APE 15% by using 2,3,4 points,separately.Limited sampling strategies have been developed and validated for estimating AUC0?24 h of amlodipine.The present study indicated that the implemention of both 5 mg and 10 mg dosage could enable accurate predictions of AUC0?24 h by the same LSS model.This study shows that 12,4,24,2 h after administration are key sampling time points.The combination of(12,4),(12,4,24) or(12,4,24,2 h) might be chosen as sampling hours for predicting AUC0-24 h in practical application according to requirement.展开更多
文摘目的研究乳腺癌患者化疗后,多西他赛(docetaxel,DTX)药时曲线下面积(area under curve,AUC)与血液学毒性(中性粒细胞减少)的相关性,为患者个体化给药提供理论依据。方法选择郑州大学附属肿瘤医院2016年12月—2017年7月接受AC序贯T化疗方案的94例乳腺癌患者,采用胶乳免疫比浊法测定患者静脉输注DTX后的血药浓度,并通过非混合效应模型软件计算多西他赛AUC。建立利用AUC预测化疗后中性粒细胞减少百分比的数学模型。结果多西他赛AUC在(0.7~3.9)mg·h/L之间,平均值为(2.34±0.7)mg·h/L,患者间AUC的变异系数(CV%)为30%。出现低级别(0~2级)及高级别(3~4)中性粒细胞减少的AUC平均值分别为2.29 mg·h/L和2.82 mg·h/L(P=0.003)。利用多西他赛AUC预测中性粒细胞减少百分比的模型为y=-1.8672x^2+25.658x-14.92,r=0.643。结论本研究建立的利用AUC预测中性粒细胞减少百分比的数学模型,为通过测定患者AUC进行多西他赛个体化的给药提供了理论依据。
文摘盐酸金霉素广泛应用于家畜和家禽,然而,金霉素的低溶解度限制了其应用。该试验以20 mg/kg单剂量灌服盐酸金霉素和超级金霉素,采集各时间节点的血浆样品并用UPLC/MS/MS检测其血药浓度,计算各种药动学参数,评估盐酸金霉素和超级盐酸金霉素在肉鸡体内的ADME(Absorption distribution metabolism excretion)过程。结果表明:单剂量给药后超级盐酸金霉素的峰浓度显著高于盐酸金霉素[(4.69±1.54)μg/mL vs (1.91±0.63)μg/mL],表明超级盐酸金霉素的吸收速度快于盐酸金霉素。超级盐酸金霉素的药时曲线下面积(AUC)(Area under the concentration-time curve, AUC)也大于盐酸金霉素[(14.51±3.40) hr·μg·mL^(-1)vs (6.28±2.69) hr·μg·mL^(-1)]。表明超级盐酸金霉素到达全身血液循环的量多于盐酸金霉素,有利于提高金霉素的药效。以20 mg/kg剂量连续灌服盐酸金霉素和超级盐酸金霉素7 d后,检测肌肉和肝脏中盐酸金霉素和超级盐酸金霉素的残留量接近或低于检测限,远低于食用动物肌肉中盐酸金霉素的残留限量。因此,超级盐酸金霉素提高了盐酸金霉素的生物利用度,具有广阔的应用前景和推广价值。
文摘This study aims to save cost of sampling for estimating the area under the amlodipine plasma concentration versus time curve in 24 hours(AUC0?24 h).Limited sampling strategy(LSS) models was developed and validated by mutilple regression model within 4 or fewer amlodipine concentration values.Absolute prediction error(APE),root of mean square error(RMSE) and visual predict check were used as criterion.The results of Jackknife validation showed that fifteen(9.4%) of the 160 LSS based on regression analysis were not within an APE of 15% by using one concentration-time point.156(97.5%),159(99.4%) and 160(100%) of the 160 LSS model were capable of predicting within an APE 15% by using 2,3,4 points,separately.Limited sampling strategies have been developed and validated for estimating AUC0?24 h of amlodipine.The present study indicated that the implemention of both 5 mg and 10 mg dosage could enable accurate predictions of AUC0?24 h by the same LSS model.This study shows that 12,4,24,2 h after administration are key sampling time points.The combination of(12,4),(12,4,24) or(12,4,24,2 h) might be chosen as sampling hours for predicting AUC0-24 h in practical application according to requirement.
