Steinijans V W, Hartmann M, Huber R, Radtke H W
Department of Biometry, Byk Gulden Pharmaceuticals, Konstanz, Germany.
Int J Clin Pharmacol Ther Toxicol. 1991 Aug;29(8):323-8.
The demonstration that concomitant administration of drug B does not affect the pharmacokinetics of drug A can be adequately handled as an equivalence problem. Administration of drug A alone serves as reference and simultaneous administration of drugs A and B as test situation. The range of clinically acceptable variation in the pharmacokinetic characteristics of drug A defines the equivalence range. This will usually correspond to the bioequivalence range accepted for the comparison of different formulations of drug A. Equivalence, i.e. lack of pharmacokinetic interaction, is concluded if the 90%-confidence interval for the ratio (difference) of the expected medians for test and reference is entirely within the equivalence range. This decision procedure ensures that the consumer risk of incorrectly concluding "lack of interaction" is limited to 5%. Moreover, the producer risk of incorrectly concluding "interaction" can be controlled by appropriate sample sizes.
药物B与药物A同时给药不影响药物A的药代动力学这一证明可作为一个等效性问题来充分处理。单独给予药物A作为对照，同时给予药物A和药物B作为试验情况。药物A药代动力学特征的临床可接受变异范围定义了等效范围。这通常将对应于用于比较药物A不同制剂所接受的生物等效性范围。如果试验组与对照组预期中位数之比（差值）的90%置信区间完全在等效范围内，则可得出等效性结论，即不存在药代动力学相互作用。这一决策程序可确保消费者错误得出“无相互作用”结论的风险限制在5%。此外，通过适当的样本量可控制生产者错误得出“有相互作用”结论的风险。
