液-质联用法测定中年妇科病人咪达唑仑及其代谢物的血药浓度并研究其细胞色素P450 3A4酶活性分布特征

目的 研究中年妇科手术病人应用咪哒唑仑(抗焦虑药)及其CYP3A_4酶活性分布特征.方法 以咪哒唑仑作为探针药物,用液-质联用法测定血桨中咪达唑仑、1'-羟基咪达唑仑的单点药物浓度,以1'-羟基咪达唑仑/咪达唑仑的比值评估CYP3A4酶活性.结果 260例妇科手术病人CYP3A4酶的活性为0.46±0.14,推测中年妇科手术病人CYP3A4酶活性的正常值范围为0.18～0.73.结论 CYP3A4酶活性在中年妇科手术病人中呈正态分布,酶活性的个体差异较小,对术后的个体化药物治疗影响不大.

Determinaton the concentration of midazolam and its metabolites in gynaecologic surgical patients and study the distribution of CYP3A4 activity by LC-MS

Objective To study the distribution of CYP3A4 activity in 260 middle-aged gynaecologic surgical patients. Methods Midazolam (MDZ) is used as a probe of eytoehrome P450 3A4 (CYP3A4) activity by a single-point blood measurement. CYP3 A4 activity was measured by plasma ratio of 1'-hydroxymidazolam and midazolam using LC/ MS. Result The mean value of CYP3A4 activity in 260 middle-aged gynaecologic patients (aged 30-50 years) measured was 0. 46 ±0. 14 and 95% confidence interval for mean was 0. 43-0. 48. The range for normal value is 0. 18-0. 73. Conclution CYP3A4 activity is mormal distribution observed in gynaecologic patients. CYP3A4 activity variation has a little effect on the metabolism of commonly used drugs after surgery that are substrates for this enzyme.