Alteration of UDP-glucuronosyltransferase 1a1, 1a7 and P-glycoprotein expression in hepatic fibrosis rats and the impact on pharmacokinetics of puerarin.

BACKGROUND: Puerarin, derived from a traditional Chinese herb Pueraria lobata (Willd.) Ohwi which was distributed globally and planted in most parts of China, has been extensively applied in patients with cardiovascular diseases in China. Yet a considerable proportion of the patients were accompanied with liver illnesses simultaneously because of all sorts of reasons. HYPOTHESIS/PURPOSE: It had been implied by some previous research that the absorption and the metabolism of puerarin were susceptible to liver issues due to changed P-gp and Ugt1a level, but pharmacokinetics of puerarin under such conditions were few concerned. Our study aimed to make sure whether and how much the behavior of puerarin in vivo was affected by hepatic diseases, and to explore the potential mechanisms. METHODS: A CCl4 induced rat model of hepatic fibrosis (HF) was prepared and verified. Single low/high doses of oral and intravenous administration of puerarin to HF and normal rats were performed. Pharmacokinetics of puerarin were determined by a validated HPLC method. The expression of P-gp, Ugt1a1, and Ugt1a7 in both liver and intestines were determined by quantitative RT-PCR and Western blot analysis respectively. RESULTS: The systemic exposure of puerarin in HF rats of experimental groups were found decreased remarkably except for that of the high dose intravenous group. Moreover, the expression of P-gp, Ugt1a1, and Ugt1a7 in liver and intestines of HF rats were figured out increased. CONCLUSION: The results indicated that the HF originated overexpression of Ugt1a1, Ugt1a7, and P-gp level played important roles in pharmacokinetics of puerarin, suggested the clinical regimen of puerarin based on normal populations might be inappropriate for patients with chronic liver diseases. It was implied drugs whose absorption or elimination were related to P-gp, Ugt1a1, or Ugt1a7 might also be affected by hepatic illnesses.

[Observation on effect of compound danshen droplet-pill combined with trimetazidine in treating senile unstable angina pectoris].

OBJECTIVE: To investigate the effect of compound Danshen Droplet-pill (DS) combined with trimetazidine (TMZ) in treating senile unstable angina pectoris (SUAP). METHODS: One hundred and twenty patients with SUAP were eaually and randomly divided into 2 groups, the treated group and the control group. Changes of angina, occurrence of arrhythmia, myocardial infarction and sudden death, myocardial ischemia in ECG and partial indexes of heart function were observed. RESULTS: The total effective rate in the treated group was 78.3%, while that in the control group was 53.3%, comparison of the two groups showed significant difference (P < 0.05). The incidence rate of arrhythmia in the two groups was 18.2% and 30.0% respectively and that of acute myocardial infarction and sudden death was 0 and 5.0% respectively, also showed significant difference between them (P < 0.05). Condition of myocardial ischemia revealed in ECG and partial indexes of heart function in the treated group were all improved to certain extent. Conclusion DS combined with TMZ is superior in treating SUAP.