Zhang Juanling, Zhu Junbo, Yao Xingchen, Duan Yabin, Zhou Xuejiao, Yang Meng, Li Xiangyang
College of Eco-Environmental Engineering, Qinghai University, Xining, China.
Pharmacology. 2016;97(3-4):107-13. doi: 10.1159/000443332. Epub 2016 Jan 6.
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 t(1/2) 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.
为研究细胞色素P450 3A4（CYP3A4）代谢的盐酸利多卡因在低海拔地区生活的中国汉族志愿者以及高海拔地区的中国汉族和藏族本土志愿者体内的药代动力学，将10 mg盐酸利多卡因通过肌肉注射给予3组人群：低海拔地区生活的汉族志愿者、高海拔地区的汉族和藏族本土志愿者。在给予研究药物（基线）前以及给药后0.25、0.5、1.0、1.5、2.0、3.0、4.0、6.0、8.0小时采集血样。采用反相高效液相色谱法测定血浆中的盐酸利多卡因。盐酸利多卡因的药代动力学参数显示，汉族和藏族本土志愿者之间无显著差异，但这两组的t(1/2)分别比低海拔组高29.8%和29.8%。为研究相关机制，在大鼠中检测了慢性高原低氧暴露对CYP3A1活性和表达的影响。大鼠分为低海拔组、慢性中度高原低氧组和慢性高原低氧组。慢性高原低氧导致大鼠体内CYP3A1的活性、蛋白和mRNA表达显著降低。本研究发现，与低海拔地区的健康汉族受试者相比，高海拔地区的藏族和汉族健康受试者体内盐酸利多卡因的处置有显著变化，这可能是由于慢性高原低氧条件下CYP3A4的活性、蛋白和mRNA表达显著降低所致。
