摘要
目的：观察正常人口服泛昔洛韦片剂的剂量耐受性、药动学和生物利用度，提出安全的临床治疗剂量。方法：４ 组（ 每组６ 人）健康人分别口服０－１２５ｇ 、０－２５ｇ 、０－５ｇ 、０－７５ｇ 泛昔洛韦片剂，进行剂量耐受性试验。用ＨＰＬＣ 法测定９ 人分别口服国产和进口的泛昔洛韦（ｆａ ｍｃｉｃｌｏｖｉｒ） 片各０－２５ｇ 后血和尿的喷昔洛韦（ｐｅｎｃｉｃｌｏｖｉｒ） 浓度。结果：口服０－１２５ｇ ～０－７５ ｇ 泛昔洛韦片剂呈现良好的耐受性。口服０－２５ｇ 泛昔洛韦国产片除了与进口片有生物等效性外，药－ 时曲线呈二房室开放模型，约１ｈ 前达峰，Ｃｍ ａｘ ２－２０ ｍ ｇ／ Ｌ，Ｔ１／２α（１－０１ ±１－５１）ｈ ，Ｔ１／２β（２－９３ ±０－８３）ｈ ，Ｖ／Ｆ（５５－１ ±２７－８） Ｌ，２４ｈ 尿喷昔洛韦累积率为（６６－３ ±１５－３） ％ 。结论：国产泛昔洛韦片口服后具有吸收较快、喷昔洛韦在体内分布迅速而广泛、大部分经肾排泄的特点。单剂量口服泛昔洛韦良好的耐受性和药动学特点的事实，推荐口服泛昔洛韦０－１２５ｇ ～０－７５ｇ 、１ 日３ 次的给药方案用于临床可能是安全的。
AIM:To make sure safe famciclovir dose by experiment of dose tolenance and pharmacokinetics METHODS:Domestic famciclovir tablets in a single dose(0.125、0.25、0.5 and 0.75g)were orally administered to 4 groups(3♂ and 3♀ in each group) of healthy volunteers,respectively,to observe dosage tolerance.The contents of penciclovir in plasma and urine were determined by HPLC method after 0.25g domestic famciclovir tablet and Famvir(famciclovir) tablet were orally given to 9 male healthy subjects with randomized-cross and auto-paired method,respectively RESULTS:The volunteers could tolerate this medication in dose of 0.125g～0.75g.No toxic reactions and abnormal results of experimental tests were found.The major pharmacokinetic characteristics were as follows C-T curve of penciclovir displayed open two-comparment model.Penciclovir peak concentration might reach within one hour following administration T1/2ka:(0.15±0.08)h,Cmax:(2.20±0.39)mg/L,T1/2α:(1.01±1.51)h,T1/2β:(2.93±0.83)h,V/F:(55.1±27.8)L,24h urine-accumulating excretion rate of penciclovir:(66.26±15.34)%.Pharmacokinetic parameters of Famvir and domestic famciclovir tablet about bioavailability could be described as follows:Tmax:(0.84±0.34) and( 0.93±0.40)h(P>0.05;bioequivalent test),Cmax:(2.22±0.66) and( 2.20±0.39)mg/L,AUC0～12h:(6.25±1.24) and (6.24±1.28)mg/(L·h),AUC0～∞:1.08 and 6.82±1.10mg/(L·h).The above-mentioned three parameters were no statistically significant(P<0.05;bioequivalent test),between domestic and imported products.Bioavailability of domestic famciclovir tablet was (101±15)%.CONCLUSION:Domestic famciclovir tablet has characteristics of rapid absorption,extensive distribution,mainly excreted via urine and is bioequivalent with Famvir.That fine tolerance to single dose of famciclovir and pharmacokinetic charateristics similar to Famvir showed that famciclovir in a dose of 0.125g～0.75g,3 times daily would be safe for clinical use.
出处
《中国药房》
CAS
CSCD
2000年第1期29-31,共3页
China Pharmacy
