Individual Differences in Pharmacokinetics and Pharmacodynamics of Anesthetic Agent Propofol with Regard to CYP2B6 and UGT1A9 Genotype and Patient Age
Individual Differences in Pharmacokinetics and Pharmacodynamics of Anesthetic Agent Propofol with Regard to CYP2B6 and UGT1A9 Genotype and Patient Age
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DOI：
10.2133/dmpk.dmpk-11-rg-039
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发表时间：
2011-01-01
影响因子：
2.1
通讯作者：
Yamazaki, Hiroshi
中科院分区：
文献类型：
--
作者：
Kansaku, Fumiyasu;Kumai, Toshio;Yamazaki, Hiroshi
丙泊酚（2，6-二异丙基苯酚）静脉给药用于麻醉诱导和维持;然而，已报告了与丙泊酚使用相关的进行性心肌衰竭（丙泊酚综合征）病例。在本研究中，在CYP 2B 6和UGT 1A 9基因分型的患者中研究了丙泊酚药代动力学和/或药效学的个体差异。本研究招募了51例在圣玛丽安娜大学医院接受丙泊酚治疗的患者，并提供了书面知情同意书。分析了以下参数：作为药效学参数的觉醒时间、丙泊酚输注持续时间、治疗后血浆药物浓度、CYP 2136和UGT 1A 9基因型和年龄（42-84岁，平均65岁）。由于分布和消除，丙泊酚从受试者的血液中迅速清除。在这些受试者中，停止输注丙泊酚后的觉醒时间与输注时间和丙泊酚的最大浓度显著相关。随着输注持续时间恢复正常后，丙泊酚的最大血浆浓度受CYP 2B 6 G516 T变异体（与功能受损相关）的影响，并受丙泊酚风险指数评分（包括CYP 2B 6 G516 T和UGT 1A 9 I399 C>T（高表达）基因型和高龄）的显著影响。这些结果提供了重要的信息，表明研究的两种酶的基因型和高龄是丙泊酚的药代动力学和/或药效学的组合决定因素。
Propofol (2,6-diisopropylphenol) is administered intravenously for induction and maintenance of anesthesia; however, cases of progressive myocardial failure (propofol syndrome) related to the use of propofol have been reported. In the present study, the individual differences in pharmacokinetics and/or pharmacodynamics of propofol were investigated in patients who were genotyped for CYP2B6 and UGT1A9. Fifty-one patients treated with propofol in St. Marianna University Hospital were recruited for this study and provided written informed consent. The following parameters were analyzed: awakening time as a pharmacodynamic parameter, duration of propofol infusion, drug concentration in plasma after treatment, genotypes of CYP2136 and UGT1A9, and age (42-84 years, mean of 65 years). Propofol was rapidly cleared from the blood of the subjects as a result of distribution and elimination. The awakening time after stopping propofol infusion was significantly correlated with the duration of infusion and the maximum concentration of propofol in these subjects. The maximum plasma concentration of propofol after normalizing with the duration of infusion was affected by the CYP2B6 G516T variant (related to impaired function) and was significantly affected by a propofol risk index score that incorporated CYP2B6 G516T and UGT1A9 I399C>T (high expression) genotypes and advanced age. These results provide important information indicating that the genotypes of the two enzymes studied and advanced age are combinative determinant factors of the pharmacokinetics and/or pharmacodynamics of propofol.