Pharmacokinetics Studies On Hymecromone In Rabbits

Hymecromone, the chemical name is 7- hydroxy -4- methyl-2H-1-Benzopyran-2- ketone, is widely used in industry, agriculture, medicine and other fields. In the ield of medicine, hymecromone are primarily used as a choleretic drug for the treatment of cholecystitis, cholelithiasis, biliary tract infections, gallbladder surgery syndrome, etc. A monomer which has a highly efficient of acaricidal activity has benn extracted from Artemisia scoparia Walds et kit, and it was identified as hymecromone. Hymecromone is insoluble in water and fat, its sodium salt was used in pharmacokinetics studies on hymecromone in humans and rats abroad. In this study, the hymecromone sodium salt was synthesized firstly, and a method of determining the concentration of hymecromone of blood plasma by reversed-phase high performance liquid chromatography in rabbits was established. Then, the pharmacokinetics of hymecromone in rabbits were studied. The results were as follows:1. Synthesis of hymecromone sodium salt: Hymecromone sodium salt was prepared by reaction of hymecromone (10 mmol) with sodium hydroxide(9.5 mmol), recrystallization in the solution of 92% acetone in water provided pale yellow needle crystal with yield of 75%, The structure of the compound was characterized by TLC, UV, IR, 1H NMR, 13C NMR and MS, and was confirmed to be hymecromone sodium salt. The content of the product samples detected by the UV method was built, which the equation of standard curves was y=0.0869x-0.3011 (n=7), (R²=0.9976) and the linear relations were good in the concentration range of 5³0μg/mL, and the mean content of hymecromone sodium salt synthesized by this new process was 98%.2. A Method for determination content of hymecromone in rabbits blood plasma was established: the chromatographic conditions, which was used for determinating the content of hymecromone in rabbits blood plasma, were decided to be C18 column (4.6×150 mm, 5μm), Methanol and water (55:45) as mobile phase, 7-hydroxy coumarin as the internal standard and acetonitrile precipitation method for removing albumin with detective UV wavelength at 324 nm and column temperature at 30℃. Under these eonditions, the ratio of peak areas for hymecromone to internal standard 7-hydroxy coumarin was linear with the content of hymecromone in the range of 20³2000 ng/mL. The RSD of with-in day precision test and between-day precision test (n=5)were both less 4%. The average recovery and extraction recovery was 100.02% and 95.78%. This method is sensitive, simple, accurate, fast, specific for pharmacokinetics study on hymecromone in rabbits.3. Pharmacokinetics study on hymecromone in rabbits: The pharmaeokineties study of hymecromone in rabbits was made after intravenous injection and transdermal drug delivery using RP-HPLC method. The results showed that hymecromone abided by two-compartment model in rabbits. After intravenous injection, its average pharmacokinetic equations was C=14997.19e^-3.957t+161.72e^-0.05t; the area under the plasma concentration-time curve (AUC) was 3967.28±1554.60 ng/mL·h, the distribution half-life (T_1/2α) was 0.18±0.04h, the elimination half-life (T_1/2β) was 15.99±5.25 h, the apparent volume of distribution (Vd) was 5.19±2.10 L/(h·kg). After transdermal drug delivery, its average pharmacokinetic equations was C=210.13e^-0.31+108.02e^-0.0032t-318.15e^-4.06t; AUC was 9295.16±3411.64 ng/mL·h, the absorption half-life (T1/2kα) was 0.18±0.05 h, T_1/2α was 2.27±0.24 h, T_1/2β was 54.92±14.93 h, the peak concentration (C_max) was 318.15±4367 ng/mL, Vd was 493.21±65.29 L/(h·kg), the CL was 2030.62±691.41 ng/(kg·h).