Effects of Chungsinoryungsan, a Polyherbal Complex, on the Pharmacokinetic Profiles of Perindopril in Rats

For sufficient antihypertension with less adverse effects, numerous clinical trials have recommended combination therapy using two or more hypertensive drugs. Chungsinoryungsan (CSORS) is a polyherbal complex based on oriental medicine, which has shown therapeutic potentials for antihypertension and additional renal improvement. Therefore, the affect of CSORS on the pharmacokinetic profiles of perindopril, an antihypertensive drug, was analyzed as a novel combination of hypertensive drugs. Rats received perindopril with CSORS as the combination or distilled water as the control. The co-administration of perindopril with CSORS or distilled water was performed by single dosing or repeated dosing for a week at a 2-h interval. The analyzed pharmacokinetic parameters included peak concentration (C), time to reach the C (T), area under the plasma concentration-time curve, terminal half-life (t) and mean residence time to infinity (MRT). In the single oral co-administration within 5 min, the pharmacokinetics of perindopril demonstrated an increased T and MRT but reduced t in the combination compared to the control treatment, indicating drug-drug interactions between perindopril and CSORS. However, in the repeated co-administration for a week at a 2-h interval, which was more than perindopril MRT in the control treatment (1.5±0.1 h), the initial co-administration showed no differences in the pharmacokinetics between the combination and control treatments. Furthermore, the repeated co-administration also showed no differences between the combination and control treatment. The results indicate that CSORS can be co-administered at a 2-h interval that was more than perindopril MRT and further clinical studies may provide detailed information for developing a drug regimen that generates enhanced combination effects of CSORS with hypertensive drugs.