Evodiamine decreased the systemic exposure of pravastatin in non-alcoholic steatohepatitis rats due to the up-regulation of hepatic OATPs

Ruifeng Liang; Wenjing Ge; Bingjie Li; Weifeng Cui; Xiaofan Ma; Yuying Pan; Gengsheng Li

doi:10.1080/13880209.2022.2036767

Evodiamine decreased the systemic exposure of pravastatin in non-alcoholic steatohepatitis rats due to the up-regulation of hepatic OATPs

Pharm Biol. 2022 Dec;60(1):359-373. doi: 10.1080/13880209.2022.2036767.

Authors

Ruifeng Liang^{1

2}, Wenjing Ge¹, Bingjie Li^{1

2}, Weifeng Cui¹, Xiaofan Ma¹, Yuying Pan¹, Gengsheng Li¹

Affiliations

¹ Institute of Chinese Materia Medica, Henan Provincial Academy of Traditional Chinese Medicine, Zhengzhou, China.
² School of Pharmacology, Henan University of Traditional Chinese Medicine, Zhengzhou, China.

Abstract

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 μg/L), AUC_0-t (18.17 ± 2.52 vs. 14.91 ± 2.03 mg/min/L) and AUC_0-∞ (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-1β, IL-6, and TNF-α 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.

Keywords: Drug-drug interaction; hepatic uptake; organic anion transporting polypeptide; pharmacokinetics.

MeSH terms

Animals
Area Under Curve
Herb-Drug Interactions
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
Male
Non-alcoholic Fatty Liver Disease / drug therapy*
Organic Anion Transporters / genetics*
Pravastatin / pharmacokinetics*
Quinazolines / pharmacology*
Rats
Rats, Sprague-Dawley
Up-Regulation / drug effects

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Organic Anion Transporters
Quinazolines
evodiamine
Pravastatin

Grants and funding

This work was supported by the National Natural Science Foundation of China under (81873022, 81403124) and the Chinese Medicine Research Project of Henan Province (2016ZY2022).