期刊
PHARMACEUTICAL BIOLOGY
卷 60, 期 1, 页码 359-373出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/13880209.2022.2036767
关键词
Drug-drug interaction; pharmacokinetics; hepatic uptake; organic anion transporting polypeptide
资金
- National Natural Science Foundation of China [81873022, 81403124]
- Chinese Medicine Research Project of Henan Province [2016ZY2022]
The study showed that evodiamine reduced the systemic exposure of pravastatin in NASH rats by enhancing the uptake and distribution in the liver. This was achieved by up-regulating the expression of OATPs. Additionally, evodiamine also decreased the levels of pro-inflammatory cytokines in NASH rats.
Context Patients with non-alcoholic steatohepatitis (NASH) may have a simultaneous intake of pravastatin and evodiamine-containing herbs. Objective The effect of evodiamine on the pharmacokinetics of pravastatin and its potential mechanisms were investigated in NASH rats. Materials and methods The NASH model was conducted with feeding a methionine choline-deficient (MCD) diet for 8 weeks. Sprague-Dawley rats were randomised equally (n = 6) into NASH group, evodiamine group (10 mg/kg), pravastatin group (10 mg/kg), and evodiamine (10 mg/kg) + pravastatin (10 mg/kg) group. Normal control rats were fed a standard diet. Effects of evodiamine on the pharmacokinetics, distribution, and uptake of pravastatin were investigated. Results Evodiamine decreased C (max) (159.43 +/- 26.63 vs. 125.61 +/- 22.17 mu g/L), AUC(0-t) (18.17 +/- 2.52 vs. 14.91 +/- 2.03 mg/min/L) and AUC(0-infinity) (22.99 +/- 2.62 vs. 19.50 +/- 2.31 mg/min/L) of orally administered pravastatin in NASH rats, but had no significant effect in normal rats. Evodiamine enhanced the uptake (from 154.85 +/- 23.17 to 198.48 +/- 26.31 pmol/mg protein) and distribution (from 736.61 +/- 108.07 to 911.89 +/- 124.64 ng/g tissue) of pravastatin in NASH rat liver. The expression of Oatp1a1, Oatp1a4, and Oatp1b2 was up-regulated 1.48-, 1.38-, and 1.51-fold by evodiamine. Evodiamine decreased the levels of IL-1 beta, IL-6, and TNF-alpha by 27.82%, 24.76%, and 29.72% in NASH rats, respectively. Discussion and conclusions Evodiamine decreased the systemic exposure of pravastatin by up-regulating the expression of OATPs. These results provide a reference for further validation of this interaction in humans.
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