应用黄金区域法研究减少药物不良反应和降低耐药性的方法

Study of Reducing Adverse Drug Reactions and Resistance by Gold Zone Method

目的用黄金区域法研究减少药物不良反应和降低耐药性的方法。方法考察剂量与用药效果的关系,以黄金区域为中段,把经验范围分成三段是研究设计的关键。结果超大容量样本调查表明,头孢孟多和头孢曲松分别随着按公斤体重剂量由小到大,不良反应率都由高变低,然后再升高,呈U形规律,U形的底部出现在黄金区域上。利用中心极限定理和正态分布的性质论证了在不到经验范围1/4的黄金区域内分布着将近70%的概率,机体对药物的准确适合量就在其中。耐药性与用药剂量的关系也符合U形规律。结论用黄金区域法规定用药剂量可以成为解决抗菌素被滥用、不良反应和耐药性的特殊突破口。

OBJECTIVE To reduce adverse drug reactions and resistance of cefamandole nafate for injection and ceflriaxone sodium for injection by gold zone method. METHODS The relationships between doses and effects were studied. Using gold zone as the middle range and dividing empirical range into three sections are the keypoints to the study design. RESULTS The incidences of drug adverse reactions of both drugs complied with U-shaped rule, ie, with the increase of doses （mg · kg-1· d-1 ） , the adverse reaction rates first decreased and then rose, and the bottom of the U-shaped curve was in the gold zone. Central limit theorem and normal distribution demonstrated that the appropriate doses existed in the gold zone, which was less than 1/4 of the empirical range but coverd nearly 70% of the probability. The relationship between the resistance and dose also followed U-shaped rule, and the bottom of the Ushaped curve was also in the gold zone. CONCLUSION Abuse, adverse reactions and resistance are the three major problems in antibiotics use today. Using gold zone method to determine dose may be a special breakthrough in solving these problems.