动物造模 z-bio 2022-12-09 363

　　Objective To study the pharmacokinetic differences of 7 active components of eucommia ulmoides extract after repeated administration in normal rats and spontaneously hypertensive rats, namely, pinoresinol diglucoside, geniposide, chlorogenic acid, protocatechuic acid, neochlorogenic acid, cryptochlorogenic acid and pinoresinol monoglucoside.

　　Methods Normal rats and spontaneously hypertensive rats were used as the experimental objects. The Eucommia ulmoides extract was administered by gavage at a dose of 5.4g/kg once a day for 7 consecutive days. The differences in pharmacokinetics and tissue accumulation of 7 active components in Eucommia ulmoides extract between normal rats and SHR models were compared.

　　Results The pharmacokinetic study showed that the pharmacokinetic parameters of CCA and NCA in the SHR model were not significantly different from those in the normal group. The T1/2 of PDG in SHR model group was 0.26 times of that in normal group; The T1/2, Tmax and AUC0-t of GA in SHR model group were 2.20, 0.04 and 0.50 times of those in normal group respectively; The T1/2 of PCG in SHR model group was 0.55 times of that in normal group; The T1/2 of PCA in SHR model group was 2.04 times of that in normal group; The T1/2 and AUC0-t of CA were 1.93 and 0.64 times of those of normal group respectively. Accumulation experiment results showed that seven active components, including GA, were mainly distributed in stomach, small intestine, heart, liver and lung. In addition to CCA, CA, NCA, PCA, GA, PDG and PG in SHR model were significantly different from those in normal group in terms of the number of tissues and organs with significant difference in content.

　　Conclusion The organism under the pathological state of spontaneous hypertension can significantly change the pharmacokinetics behavior of the antihypertensive active components of Eucommia ulmoides in plasma and the accumulation in tissues. For hypertensive patients who need to take drugs for a long time, the pharmacokinetics behavior of drugs in vivo is particularly important. This study can provide some reference for the long-term dosage adjustment of Eucommia ulmoides in clinical use.