摘要
目的研究健康人po盐酸伐昔洛韦片后的药动学和生物等效性。方法20个健康受试者采用随机分组自身交叉对照试验设计,口服盐酸伐昔洛韦片600 mgHPLC-MS联用法测定血浆中代谢产物阿昔洛韦浓度,以BAPP程序计算其药动学参数和评价生物等效性。结果在选定的色谱/质谱条件下阿昔洛韦与内标及血浆杂质分离良好,在41.6～5.34×103μg·L-1内线性良好。阿昔洛韦的相对回收率大于96.7%,日内和日间RSD小于10.2%。盐酸伐昔洛韦片受试制剂(T)和参比制剂(R)的主要药动学参数:tmax分别为(1.5±0.6)(T)和(1.5±0.6)h(R),ρmax分别为(2.83×103±7.76×102)(T)和(2.72×103±8.50×102)μg·L-1(R);t1/2分别为(3.21±0.29)(T)和(3.23±0.30)h(R);AUC0-14分别为(1.02×104±2.03×103)(T)和(9.91×103±2.46×103)μg·h·L-1(R);盐酸伐昔洛韦片相对生物利用度为(104.5±14.0)%。结论用LC-MS测定血浆中代谢产物阿昔洛韦浓度,杂质无干扰,定量限低,重复性好,准确度高。受试的盐酸伐昔洛韦片与参比的盐酸伐昔洛韦片生物等效。
Abstract
OBJECTIVE To study the pharmacokinetics and bioequivalence of valaciclovir in human.METHODS Twenty volunteers orally took the valaciclovir tablets with 2-way crossover design.The concentration of acyclovir,the metabolite of valaciclovir in plasma,was determined by HPLC-MS.The pharmacokinetic parameters were calculated by BAPP software.RESULTS The calibration curve was linear in the range from 41.6 to 5.34×103 μg·L-1.The relative recovery was more than 96.7%.The intra-and inter-RSDs were less than 10.2%.The main pharmacokinetic parameters of t1/2,ρmax,tmax and AUC0-14 for the test tablet were(3.21±0.29) h,(2.83×103±7.76×102) μg·L-1,(1.5±0.6) h and(1.02×104±2.03×103) μg·h·L-1,respectively.The pharmacokinetic parameters of t1/2,ρmax,tmax and AUC0-14 for the reference tablet were(3.23±0.30) h,(2.72×103±8.50×102) μg·L-1,(1.5±0.6) h and(9.91×103±2.46×103) μg·h·L-1,respectively.The relative bioavailability of the test tablet was(104.5±14.0)%.CONCLUSION The HPLC-MS method for the determination of acyclovir in plasma was proved to be sensitive,accurate and convenient.The reference and test tablets were bioequivalent.
关键词
伐昔洛韦 /
阿昔洛韦 /
高效液相色谱-质谱 /
生物等效性
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Key words
valaciclovir /
acyclovir /
HPLC-MS /
bioequivalence
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陈玟;许美娟;张军;居文政;谈恒山;刘芳.
高效液相质谱联用研究伐昔洛韦人体生物等效性[J]. 中国药学杂志, 2008, 43(21): 1647-1650
CHEN Min;XU Mei-jun;ZHNG Jun;JU Wen-zheng;TN Heng-shn;LIU Fng.
Bioequivalence Study of Valaciclovir in Human by HPLC-MS Assay [J]. Chinese Pharmaceutical Journal, 2008, 43(21): 1647-1650
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参考文献
[1] GCL2-1. The Technical Guide of Clinic Bioavailability and Bioe- quivalece Study for Chemical Medicine（化学药物制剂人体生物等效性和生物等效性研究技术指导原则）[S] . 2005：6-22.
[2] YE D M，LAN S，CHI B C，et al. Study on pharmacokinetics and bioavailability of two products of valaciclovir tablet[J] . China Pharm(中国药房)，2001，12(10)：607-608.
[3] XU X H，LI T L，ZHENG P C，et al. Bioavailability evaluation of valaeiclovir hydrochloride sustained tablets[J] . J Sichuan Univ(Medical Sciences Edition)(四川大学学报医学版)，2005，36(6)：898-899.
[4] JIANG X H，CHEN X R，CHENG Q，et al. Pharmacokinetics and relative bioavailability of valaciclovir hydrochloride tablet[J] . Chin Pharm J(中国药学杂志)，1997，32(2)：100-103.
[5] HU X，ZHANG H，XIA C H，et al. Pharmacokinetics and relative bioavailability of valaciclovir hydrochloride tablets in Chinese healthy volunteers[J] . J Fourth Military Med Univ(第四军医大学学报)，2006，27（18）：1726-1728.
[6] ZHANG D，CHEN J，WANG C Q，et al. Pharmacokinetics of sustained capsule of acyclovir after a single and multiple oral doses in dogs[J] . West Chin J Pharm Sci(华西药学杂志)，2002，17（2）：101-103.
[7] HE L，ZHU H，JIANG X H，et al. Pharmacokinetics and bioequivalent evaluation of two acyclovir tablets[J] . Chin J Clin Pharm(中国临床药学杂志)，1998，7（6）：275-277.
[8] HUANG J M，DUAN G L，CHEN J，et al. Study of relative bioavailability of aciclovir tablet in healthy volunteers[J] . Chin J New Drugs Clin Remedies(中国新药与临床杂志)，2004，23（12）：859-861.
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脚注
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