Study On Clinical Pharmacokinetics And Metabolites Of Oral Viaminate Capsules

ObjectiveTo investigate the effect of food on pharmacokinetics of oral viaminati capsules and the pharmacokinetics parameter of high middle low dose and mutiple dosing. Simultaneously to detect metabolites in the blood and urine,so to supply the foundation in clinical medication.MethodsThe LC-MS/MS was used to investigate the pharmacokinetics of viaminat following a single administration of 25mg 50mg 100mg 150mg by oral without food and 50mg after food in nine health volunteers.Then apply the method to test the pharmacokinetics parameter of mutle dosing and steady state trial. At the same time,to detct the metabolites in blood and urine of volunteers.Results:1. The plasma concentration of viaminate with oral 25mg capsules almost cannot be detected by LC-MS/MS, which has lowest detectable limit of 0.1ng/ml.2. The values of AUC_0-15 .Cmax Tmax and t_1/2 with single oral 50mg were 8.36±2.40h·ng/ml,1.36±0.74 ng/ml,3.11±1.17h and 4.47±0.78h And with 100mg were 17.23±5.79/ml, 4.28±1.19 ng/ml, 3.11±0.93h, 3.30+0.79h The same parameter with 150mg were 30.88±8.71/ml, 7.67±1.72 ng/ml, 3.78±0.78h and 4.58±4.26h.3. Mean drug-time curve express that middle(50mg) higher(100mg) high (150mg) dose had obviously linear correlation with absorption(AUC and Cmax).4. Mean drug concentration after twelve hours with 50mg administration in the evening is 17-66 folder than that in the morning.5. Cmax and AUC of single dose with food were higher than that without food(P<0.05).6. Tmax t1/2 and MRT was not affected by dose.7. The m/z is same with viaminate were detected in the blood of majority volunteers.8. 13-cis-retinoid that were detected in part of volunteers probably is the major hydrolysis metabolite of viaminate.