RP-HPLC法研究盐酸伐昔洛韦片人体生物利用度

Study on Relative Bioavailability of Valaciclovir Hydrochloride Tablet by RP-HPLC

目的建立准确度高、灵敏性好的反相高效液相色谱法(RP-HPLC)测定血浆中盐酸伐昔洛韦水解产物阿昔洛韦的浓度,以研究盐酸伐昔洛韦片在体内的药代动力学及相对生物利用度。方法采用两制剂双周期交叉试验设计,18名男性健康志愿者先后分别单剂量口服盐酸伐昔洛韦受试片剂或参比片剂300mg,采用RP-HPLC,以更昔洛韦为内标,测定血浆阿昔洛韦浓度。用3P97药代动力学程序处理血药浓度数据并计算参数,并作出生物等效性评价。结果口服盐酸伐昔洛韦受试片剂和参比片剂后的药代动力学参数AUC0-t分别为(9.87±2.48)和(9.94±2.67)(μg.h)/ml,AUC0-∞分别为(10.84±2.98)和(10.83±3.18)(μg.h)/ml;Cmax分别为(3.06±0.66)和(3.16±0.66)(μg.h)/ml;Tmax分别为(1.25±0.26)和(1.17±0.24)h。受试盐酸伐昔洛韦片剂以AUC0-t和AUC0-∞计算其相对生物利用度分别为(100.6±11.7)%和(101.7±13.3)%。结论建立的阿昔洛韦血药浓度监测方法灵敏、准确,测定结果可靠;统计分析结果表明受试制剂与参比制剂具有生物等效性。

Objective To establish an accurate and sensitive RP-HPLC method for the determination of acyclovir,the hydrolyzate of valaciclovir hydrochloride,in plasma and to evaluate its pharmacokinetic parameters and bioavailability in healthy Chinese male volunteers after a single oral dose of 300 mg valaciclovir hydrochloride test or reference tablets.Methods According to a randomized two-period crossover design,18 healthy volunteers were orally administered with 300 mg valaciclovir hydrochloride test or reference tablets,respectively.Acyclovir in plasma was determined by HPLC with ganciclovir used as internal standard,and the data were processed with 3P97 pharmacokinetic program.Results The pharmacokinetic parameters of the two tablets were as follows：AUC0-t was（9.87±2.48） and（9.94±2.67）（μg·h）/ml;AUC0-∞ was（10.84±2.98） and（10.83±3.18）（μg·h）/ml;Cmax was（3.06±0.66） and（3.16±0.66）（μg·h）/ml;Tmax was（1.25±0.26） and（1.17±0.24） h,respectively.The mean relative bioavailability was（100.6±11.7）%（AUC0-t） and（101.7±13.3）%（AUC0-∞） respectively.Conclusion The established RP-HPLC method was sensitive and accurate,and the pharmacokinetic parameters determined were reliable.The statistical results showed that the test and reference tablets of valaciclovir hydrochloride were bioequivalent.