内源性药物碘制剂的生物等效性研究

目的: 以卵磷脂络合碘的人体生物等效性研究为例,探讨内源性药物的生物等效性研究方法。方法: 对内源性及其他来源(饮食性)的碘进行控制。24名健康受试者进行双周期、双交叉、单剂量口服9片卵磷脂络合碘试验品和参比品,采用砷铈催化分光光度法测定血、尿中碘的浓度,用DAS2.1.1软件计算药动学参数,并进行生物等效性检验。结果: 试验品与参比品的血碘平均净浓度增加值分别为 16.8%和 19.0%,尿碘回收率分别为 84.5%和 83.3%。计算同一周期的尿碘净排泄量,用尿碘累积净排泄量(Ae_0-t)、最大净排泄速率(R_max)进行生物等效性分析。本实验研究表明卵磷脂络合碘受试制剂与参比制剂具有生物等效性。结论: 具有生物自稳定机制的内源性药物的生物等效性研究,实验设计更加复杂,各种内外因素对结果影响较大,需要尿药浓度结合背景扣除。

Bioequivalence study of endogenous drugs by iodine preparations

AIM: To study the bioequivalence of endogenous drug of iodized lecithin. METHODS: The endogenous and other sources (diet) iodine need to be controled. By a two-period cross-over tria1, a total of 24 healthy volunteers were randomized to two groups to receive 9 iodized lecithin tablets (test or reference formulation). The concentrations of iodized lecithin in serum or urine were determined by arsenic-cerium catalytic spectrophotometric method. The pharmacokinetic parameters were measured by DAS2.1.1 software.RESULTS: The value added of the average net concentration of blood iodine are 16.8% (test formulation) and 19.0% (reference formulation), and the recovery rate of urinary iodine are 84.5% and 83.3%.The net excretion of urinary iodine were subtracted from the amount obtained on the drug dosing day, and the bioequivalence analysis was done according to the baseline-adjusted parameters (Ae_{0-24 h}: cumulative urinary excretion from 0 to 48 hours,R_max: maximal rate of urinary excretion). The test and reference preparations of iodized lecithin were bioequivalent.CONCLUSION: It is a complicated design for the study of the bioequivalence of endogenous drug. Various kinds of in vivo and in vitro factors have a great influence on the result, and background need to be deducted.