Pharmacokinetics Of Yaotongning Capsule After Intragastric Administration In Rats

Yaotongning capsule is a pure Chinese compound recipe, which is effective in activating the channels, alleviating pain, reducing swelling, clearing damp and warming channels. It has been widely used to treat lumbar disc herniation, lumbar hyperostosis, sciatic neuralgia, lumbar muscle strain, and such cervical vertebra diseases for decades. As the sovereign drug of Yaotongning, Semen Strychni has intense pharmacological effects and violent toxicity.The lack of pharmacokinetics research and data has seriously retarded the clinical application of Yaotongning capsule. As the main effective ingredients of Semen Strychni, brucine and strychnine were selected as detection target to study the pharmacokinetics of Yaotongning capsule after ig (intragastric administration) in rats. The primary contents and results were as follows:(1) Established the RP-HPLC (reversed phase high performance liquid chromatography) analysis method of brucine and strychnine in rat plasma through optimizing extraction approach, concrete extracting process and solvent. Both brucine and strychnine’s recoveries in different quality control concentrations surpassed60%, also intra-day and inter-day RSDs were lower than15%, and other validation indexes like stability or linearity, all met the requirements of bioanalytical method;(2) The kinetic processes of brucine and strychnine were all in accordance with two-compartment open model after ig Yaotongning Capsule. The parameters of brucine and strychnine were as follows:T1/2α were14.03min and17.22min, T1/2P were471.97min and639.31min, T1/2Ka were5.397min and4.598min, AUCo-∞) were16555(ng/mL) min and58015(ng/mL) min, MRT(o-∞) were513.87min and746.94min, respectively. Brucine assimilated slower, eliminated faster and had inferior bioavailability than strychnine;(3) Evaluated cumulative effect of Yaotongning capsule through continuous administration to rats for10days.The main organ coefficients and drug concentration in plasma, liver or kidney of experiment group varied from control group, but there were no significant difference. To some extent, after10days administration, brucine’s concentration in plasma was obviously reduced, and strychnine in kidney was highly increased.The method is convenient and reliable, has good repeatability, precision, and stability. It can be applied to study the pharmacokinetics of Yaotongning Capsule. Continuously Yaotongning capsule administration will compromise therapeutic efficacy, thus drug resistance generates, and the renal toxicity will gradually increase. During the therapy, gradually dosage increase is recommended, and the liver function together with the renal function should be closely monitored. To explore the optimized regimen to improve the efficacy and safety of Yaotongning capsule, further expanded pharmacokinetic/pharmacodynamic synchronous analysis research must be conducted, and the relationship between administration time and dosage or therapeutic efficacy need explicitly established.