Dosage Tolerance,Pharmacokinetics and Bioavailability of Famciclovir Tablet

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(P0.05;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(P0.05;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.