泛昔洛韦胶囊和片剂的药代动力学及人体相对生物利用度研究

PHARMACOKINETICS AND RELATIVE BIOAVAILABILITY OF FAMCICLOVIA CAPSULE AND FAMCICLOVIA TABLET

9名男性健康志愿者采用拉丁方设计 ,自身对照方法分别单次口服泛昔洛韦国产胶囊、国产片及进口片剂各250mg。结果 ,口服三种制剂的泛昔洛韦250mg 后 ,喷昔洛韦的体内过程符合二房室模型。喷昔洛韦国产胶囊、国产片及进口片剂的达峰时间 (Tmax)分别为0.47±0.13h ,0.93±0.40h及0.84±0.34h ,峰浓度 (Cmax)分别为2.34±0.47mg·L-1,2.20±0.39mg·L-1 及2.22±0.66mg·L-1,药时曲线下面积 (AUC0 -12h)分别为5.88±0.71mg·h·L-1,6.24±1.28mg·h·L-1 及6.25±1.24mg·h·L-1,AUC0 -∞分别为6.98±0.96mg·h·L -1 ,6.82±1.10mg·h·L -1及7.08±1.08mg·h·L -1。末端消除相半衰期 (T1/2β)分别为3.07±0.43h ,2.93±0.83h及2.97±0.72h。24h尿中喷昔洛韦累积排泄率分别为67.1±14.6 % ,64.6±11.5 %及64.3±10.1 %。经方差分析 ,三制剂间主要药代动力学参数除Tmax 外 ,差异均无显著性 (P>0.05)。泛昔洛韦国产胶囊相对生物利用度为95.7±11.7 % ,国产片相对生物利用度为100.8±15.2 %。国产胶囊与进口片剂相比 ,AUC0 -12、AUC0 -∞ 均具有生物等效性 (双侧P<0.05) ,国产片与进口片剂相比 ,Cmax 、AUC0 -12、AUC0 -∞均具有生物等效性 (双侧P<0.05)。

A single oral dose 250 mg of domestic famciclovir capsules, domestic famciclovir tablets or imported famciclovir tablets was given to 9 healthy male volunteers at 1 week intervals in a three-way randomized cross-over design, blood samples and urine samples were withdrawn up to 12 h and 24 h, respectively. Famciclovir was deacetylated and oxidized rapidly to form penciclovir after oral administration. Plasma and urine concentrations of penciclovir were determined with HPLC. Two-compartment model with first order absorption was fitted to the concentration-time profiles of these three preparations. The results showed that the mean Tmax of these three preparations were 0.47±0.13 h,0.93±0.40 h and 0.84±0.34 h ; Cmax were 2.34±0.47 mg·L-1,2.20±0.39 mg·L-1 and 2.22±0.66 mg·L-1 ; the plasma half-lives (T1/2β)were about 3 hours; and AUC0-12h were 5.88±0.71 mg·h·L-1,6.24±1.28 mg·h·L-1 and 6.25±1.24 mg·h·L-1,AUC0-∞ were 6.98±0.96 mg·h·L-1,6.82±1.10 mg·h·L-1 and 7.08±1.08 mg·h·L-1, respectively. The accumulating excretion rate of penciclovir in urine in 24 h were 67.1±14.6%,64.6±11.5% and 64.3±10.1% respectively. There was no statistically difference (P>0.05) among these three preparations in the above parameters except Tmax. The relative bioavailability of domestic capsule and domestic tablet was 95.7±11.7% and 100.8±15.2% respectively, the result of two one-sided test suggest that these two domestic preparations are bioequivalence with the imported tablet.