Niioka Takenori
Department of Pharmacy, Hirosaki University Hospital.
Yakugaku Zasshi. 2011 Mar;131(3):407-13. doi: 10.1248/yakushi.131.407.
Cytochrome P450 (CYP) 2C19 (CYP2C19) genotype is regarded as a useful tool to predict area under the blood concentration-time curve (AUC) of proton pump inhibitors (PPIs). In our results, however, CYP2C19 genotypes had no influence on AUC of all PPIs during fluvoxamine treatment. These findings suggest that CYP2C19 genotyping is not always a good indicator for estimating AUC of PPIs. Limited sampling strategies (LSS) were developed to estimate AUC simply and accurately. It is important to minimize the number of blood samples because of patient's acceptance. This article reviewed the usefulness of LSS for estimating AUC of three PPIs (omeprazole: OPZ, lansoprazole: LPZ and rabeprazole: RPZ). The best prediction formulas in each PPI were AUC(OPZ)=9.24 x C(6h)+2638.03, AUC(LPZ)=12.32 x C(6h)+3276.09 and AUC(RPZ)=1.39 x C(3h)+7.17 x C(6h)+344.14, respectively. In order to optimize the sampling strategy of LPZ, we tried to establish LSS for LPZ using a time point within 3 hours through the property of pharmacokinetics of its enantiomers. The best prediction formula using the fewest sampling points (one point) was AUC(racemic LPZ)=6.5 x C(3h) of (R)-LPZ+13.7 x C(3h) of (S)-LPZ-9917.3 x G1-14387.2×G2+7103.6 (G1: homozygous extensive metabolizer is 1 and the other genotypes are 0; G2: heterozygous extensive metabolizer is 1 and the other genotypes are 0). Those strategies, plasma concentration monitoring at one or two time-points, might be more suitable for AUC estimation than reference to CYP2C19 genotypes, particularly in the case of coadministration of CYP mediators.
细胞色素P450（CYP）2C19（CYP2C19）基因型被视为预测质子泵抑制剂（PPI）血药浓度-时间曲线下面积（AUC）的有用工具。然而，在我们的研究结果中，CYP2C19基因型在氟伏沙明治疗期间对所有PPI的AUC没有影响。这些发现表明，CYP2C19基因分型并不总是评估PPI的AUC的良好指标。有限采样策略（LSS）被开发出来以简单而准确地估计AUC。由于患者的接受度，尽量减少血样数量很重要。本文综述了LSS在评估三种PPI（奥美拉唑：OPZ、兰索拉唑：LPZ和雷贝拉唑：RPZ）的AUC方面的实用性。每种PPI的最佳预测公式分别为AUC(OPZ)=9.24 x C(6h)+2638.03、AUC(LPZ)=12.32 x C(6h)+3276.09和AUC(RPZ)=1.39 x C(3h)+7.17 x C(6h)+344.14。为了优化LPZ的采样策略，我们试图根据其对映体的药代动力学特性，利用3小时内的一个时间点建立LPZ的LSS。使用最少采样点（一个点）的最佳预测公式为AUC(消旋LPZ)=6.5 x (R)-LPZ的C(3h)+13.7 x (S)-LPZ的C(3h)-9917.3 x G1-14387.2×G2+7103.6（G1：纯合子广泛代谢者为1，其他基因型为0；G2：杂合子广泛代谢者为1，其他基因型为0）。这些在一或两个时间点进行血浆浓度监测的策略，可能比参考CYP2C19基因型更适合用于AUC估计，特别是在联合使用CYP介导剂的情况下。
