愈美干混悬剂在健康志愿者体内的生物等效性研究

Study on bioequivalence of dextromethorphan-guaifenesin suspension and tablet in healthy volunteer

目的:建立高效液相色谱-荧光法(HPLC-FD)测定血浆中氧去甲右美沙芬1和愈创木酚甘油醚2的血药浓度,并研究愈美干混悬剂的相对生物利用度及生物等效性。方法:20名健康志愿者分两组,随机、交叉口服单剂量愈美干混悬剂(受试制剂)和愈美片(参比制剂),HPLC法测定血药浓度,计算药代动力学参数及生物等效性评价。结果:受试制剂与参比制剂血浆中氧去甲右美沙芬的T1/2:(4.13±0.87)h和(3.48±1.18)h;Cmax:(1 136.79±242.38)ng/ml和(1 069.79±237.26)ng/ml;Tmax:(1.65±0.33)h和(2.08±0.44)h;AUC0-t:(5 893.07±938.43)ng.h/ml和(5 601.46±873.04)ng.h/ml;愈创木酚甘油醚的T1/2:(0.88±0.10)h和(0.86±0.23)h;Cmax:(1 495.27±319.32)ng/ml和(1 432.73±296.47)ng/ml;Tmax:(0.61±0.13)h和(0.71±0.12)h;AUC0-t:(2 091.43±413.87)ng.h/ml和(2 056.16±424.27)ng.h/ml。愈美干混悬剂的相对生物利用度氧去甲右美沙芬为(105.60±9.90)%,愈创木酚甘油醚为(102.10±6.80)%。结论:两制剂生物等效。

Objective：To determine dextrophan and guaifenesin concentrations in human blood plasma and to study the pharma-cokinetics and relative bioavailability of dextromethorphan and guaifenesin suspension and its tablet. Methods ： A single dose of reference tablet and test suspension was given to 20 healthy volunteers in a randomized, two - way cross - over study. The plasma dextrophan and guaifenesin concentrations were determined by HPLC and detected by . fluorimetry. The pharmacokinetic parameters and relative bioavailability were measured. Results ： T1/2 of dextrophan was （4.13± 0.87 ） h and （3.48 ± 1.18 ） h for the test and the reference, respectively;Cmax was （ 1 136.79 ±242.38） ng/ml and （ 1 069.79 ± 237.26） ng/ml for the test and the ref- erence, respectively; Tmax ： was （1.65 ± 0.33） h and （2.08 ± 0.44） h for the test and the reference, respectively;AUC0-t, was （ 5 893.07 ± 938.43 ） ng ± h/ml and （5 601.46 ± 873.04） ng± h/ml for the test and the reference, respectively; T1/2 of guaifenesin was （0.88 ± 0.10） h and （ 0.86 ± 0.23 ） h for the test and the reference, respectively ; Cmax ： was （ 1 495. 27 ± 319. 32 ） ng/ml and （1 432.73 ±296.47） ng/ml for the test and the reference, respectively ;Tmax： was （0.61 ±0.13） h and （0.71 ± 0.12） h for the test and the reference, respectively;AUC0_t ： was （2 091.43 ±413.87） ng ± h/ml and （2 056.16 ±424.27）mg ·h/ml for the test and the reference, respectively. Two formulations were bioequivalent. Conclusion： The reference and the test preparations were bioequivalent.