摘要
为调查研究我国健康志愿者的药物羟化代谢缺陷频发率及与遗传的关系,本实验应用气相色谱技术,测定了145位汉族志愿者一次口服10mg异喹胍(DB)后6h尿中异喹胍和4羟异喹胍(4-OH-DB)的含量。实验结果表明,DB和4-OH-DB的比值的常用对数B(Log MR)的分布范围为-0.68-1.63(MR为0.21-43.00),DB羟化代谢具有双态性,145位志愿者中发现一位弱代谢者,其缺陷频发率为0.69%。吸烟和性别对羟化代谢的比值无明显影响。6位汉族健康志愿者的药代动力学研究表明,DB和4-OH-DB的消除半衰期(t1/2)分别为2.96±O.54和2.76±0.78h;排泄速率常数(K)分别为0.2415±0.0559和0.2641±o.0559h^(-1)。DB和4-0H-DB的最大平均排泄速率时间均为1.67h,说明DB口服吸收迅速,并可能存在“体循环前代谢”。
The polymorphism of debrisoquine hydroxylation wasstudiedin 145 unrelated, randomly selected, native healthy Han volunteersfrom 23 provinces and cities of China. The concentration of debrisoquine[DB] and 4-hydroxydebrisoquine [4-OH-DB] were determined by using GasChromatography in urines of 6 h after a single dose of 10 mg debrisoquinewas given to the volunteers. The frequency distribution of the logarithmi-cally transformed data was bimodal with an antimode at log MR=1. 10;The frequency of poor metaboliser phenotype of debrisoquine hydroxyla-tion was about 0.69% (one poor metaboliser out of 145 individuals). Nei-ther sex nor smoking habits affected debrisoquine hydroxylation in thepopulation (P<0.05). In 6 of our extensive metabolisers after a single oral dose of 10 mg DBwas given, t1/2 of DB and 4-OH-DB were 2 .96±0.54 h and 2.76±0.78 hrespectively while K of DB and 4-OH-DB were 0 .2415±0 .0539/h and0 .2641±0 .0559/h respectively; The average maximum excretion rate to DBand 4-OH-DB were both 1 .67 h which suggested the quick absorption andpresystemic metabolism of DB.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
1989年第1期56-63,共8页
The Chinese Journal of Clinical Pharmacology
基金
中国自然科学基金
关键词
异喹胍
羟化代谢
缺陷
药代动力学
debrisoquine [DB]
4-hydroxy-debrisoquine [4-OH-DB]
hydroxylation
phenotype
metabolic difficiency
half-life of elimination (t1/2)
excretion rate constant [K]
the maximum average excretion rate (Vmax)
