The Pharmacokinetic Effect Of Wu Zhi Capsules Or Diammonium Glycyrrhizinate Capsules Act Lamivudine Tablets

OBJECTIVESTo study the pharmacokinetic effect of wu zhi capsules or diammonium glycyrrhizinate capsules act lamivudine tablets,offer information for medicine rational used.To research the effect mechanism initially by animal experiment.METHODS1.A randomized,crossover,Latin square study with three phases and a washout period of 15 days was carried out.12 volunteers each took diammonium glycyrrhizinate capsules(3 pills),wu zhi capsules(2 pills)or blank capsules(2 pills)for 7 days,on the seventh day took lamivudine tabiets(100mg).Samples were collected before and at 0.25,0.5,0.75,1,1.5, 2,3,4,6,8,10,12,16,24 h after the doses of lamivudine.Plasma concentration of lamivudine was determined by HPLC-UV.To calculate and compare pharmacokinetic parameter.2.24 rats was divided into 4 groups.Intestine loop in situ technique was used to investigate the uptake rate Ke and content of lamivudine after a series of concentration(0.125,0.25,0.50mg/mL)wu zhi capsules intragastric administration.The absorption content in different groups were compareRESULTS 1.Pharmacokinetic parameters of lamivudinelamivudine:t_max:0.83±0.36 h,C_max:1458.2±350.4 ng·mL^-1,AUC_0～12: 4310.2±911.7 ng·h·mL^-1,t_1/2:2.59±0.54 h,CL/F:23.7±4.8 L·h^-1; MRT:3.0±0.4 h。2.The pharmacokinetic effect of wu zhi capsules and diammonium glycyrrhizinate capsules act lamivudineThe pharmacokinetic effect of wu zhi capsules act lamivudine.For lamivudine,t_maxshortened(P＜0.05),the parameters of C(max),t_1/2,AUC_0～12,CL/F showed no statistical change(P＞0.05).The pharmacokientic effect of diammonium glycyrrhizinate capsules act lamivudine.For lamivudine,the parameters of t_max,C_max,t_1/2,AUC_0～12,CL/F,showed no statistical change(P＞0.05).3.The effect of wu zhi capsules act on rats intestine absorbing lamivudine in intestine loop in situ techniqueWhen the intestine loop medicine concentration was 400μg·mL^-1, absorbed dose of small intestine absorbed lamivudine was 5.69±1.05mg in 3 hours,average absorptivity was 14.1±2.2%,Ka was 7×10^-4。The absorbed dose and average absorptivity of high and low groups of wu zhi capsules were more than blank group,but the parameters showed no statistical change(P＞0.05).CONCLUSIONS1.The single-dose pharmacokinetics of lamivudine in Chinese healthy volunteers was similar to that reported by foreign investigators.2.Diammonium glycyrrhizinate capsules had no significant effect on the sigle-dose pharmacokinetic parameters of lamivudine,it meaned those tow drugs could be combined safely on the point of view of pharmacokinetics. Wu zhi capsules significantly increased t_maxof lamivudine,and it had no significant effect on C_max,t_1/2,AUC_0～12and CL/F,it meaned Wu zhi capsules could speed up lamivudine's absorption process.3.The mechanism of Wu zhi capsules speed up lamivudine's absorption couldn't confirm by Wu zhi capsules increasing intestina parva permeability.