Pharmacokinetics of Lidocaine Hydrochloride Metabolized by CYP3A4 in Chinese Han Volunteers Living at Low Altitude and in Native Han and Tibetan Chinese Volunteers Living at High Altitude
Pharmacokinetics of Lidocaine Hydrochloride Metabolized by CYP3A4 in Chinese Han Volunteers Living at Low Altitude and in Native Han and Tibetan Chinese Volunteers Living at High Altitude
复制标题
CYP3A4代谢的盐酸利多卡因在低海拔汉族志愿者和高海拔汉族、藏族志愿者体内的药代动力学
作者：
张娟玲;朱俊博;姚星辰;段雅彬;周雪姣;杨梦;李向阳
为研究细胞色素P450 3A 4（CYP 3A 4）代谢的盐酸利多卡因在低海拔地区汉族志愿者和高海拔地区汉族和藏族志愿者中的药代动力学，分别对低海拔地区汉族志愿者和高海拔地区汉族和藏族志愿者肌肉注射盐酸利多卡因10 mg。在给予（基线）研究药物前和研究药物给药后0.25、0.5、1.0、1.5、2.0、3.0、4.0、6.0、8.0 h采集血样。采用反相高效液相色谱法测定血浆中盐酸利多卡因的浓度。盐酸利多卡因的药代动力学参数显示，汉族和藏族志愿者之间无显著差异，但两组的t1/2分别比LA组高29.8%和29.8%。为探讨慢性高原缺氧对大鼠细胞色素P450 3A 1活性和表达的影响，本研究采用大鼠慢性高原缺氧模型，观察慢性高原缺氧对大鼠细胞色素P450 3A 1活性和表达的影响。将大鼠分为LA组、慢性中度高原缺氧组和CHH组。CHH可使大鼠体内CYP 3A 1活性、蛋白和mRNA表达显著降低。本研究发现，与生活在LA的健康汉族受试者相比，生活在高海拔地区的本地健康藏族和汉族受试者中盐酸利多卡因的处置发生了显著变化，这可能是由于CHH条件下CYP 3A 4的活性、蛋白质和mRNA表达显著降低。
To investigate the pharmacokinetics of lidocaine hydrochloride metabolized by cytochrome P450 3A4 (CYP3A4) in Chinese Han volunteers living at low altitude (LA) and in native Han and Tibetan Chinese volunteers living at high altitude, lidocaine hydrochloride 10 mg was given by intramuscular injection to 3 groups: Han volunteers living at LA, and native Han and Tibetan volunteers living at a high altitude. Blood samples were collected before the (baseline) study drug was given and at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 h after study drug administration. Lidocaine hydrochloride in plasma was determined by RP-HPLC. Pharmacokinetics parameters of lidocaine hydrochloride showed that there were no significant difference between the native Han and Tibetan volunteers, but the t1/2 was 29.8 and 29.8% higher in 2 groups, respectively, than in the LA group. To study related mechanism, the effects of exposure to chronic high-altitude hypoxia (CHH) on the activity and expression of CYP3A1 were examined in rats. Rats were divided into LA, chronic moderate altitude hypoxia, and CHH groups. CHH caused significant decreases in the activity and protein and mRNA expression of rat CYP3A1 in vivo. This study found significant changes in the disposition of lidocaine hydrochloride in native healthy Tibetan and Han Chinese subjects living at a high altitude in comparison to healthy Han Chinese subjects living at LA, it might be due to significant decreases in the activity and protein and mRNA expression of CYP3A4 under CHH condition.
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影响因子：
7.3
作者：
Fradette, C;Bleau, AM;du Souich, P
通讯作者：
du Souich, P
影响因子：
13.5
作者：
C. Reichel;A. Nacke;T. Sudhop;G. Wienkoop;C. Luers;C. Hahn;C. Pohl;U. Spengler;T. Sauerbruch
通讯作者：
C. Reichel;A. Nacke;T. Sudhop;G. Wienkoop;C. Luers;C. Hahn;C. Pohl;U. Spengler;T. Sauerbruch
影响因子：
3.7
作者：
Wang B;Zhang YB;Zhang F;Lin H;Wang X;Wan N;Ye Z;Weng H;Zhang L;Li X;Yan J;Wang P;Wu T;Cheng L;Wang J;Wang DM;Ma X;Yu J
通讯作者：
Yu J
影响因子：
3.2
作者：
Li, Xiang-Yang;Gao, Fen;Ge, Ri-Li
通讯作者：
Ge, Ri-Li
DOI：
--
发表时间：
2015-09
期刊：
Yao xue xue bao = Acta pharmaceutica Sinica
影响因子：
--
作者：
Juan-ling Zhang;Xiang-yang Li
通讯作者：
Juan-ling Zhang;Xiang-yang Li