Herb-drug interactions: Quantitative analysis of levofloxacin absorption and transporter expression in the rat intestine following combined treatment with Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross

Yang Zhou; Mingyan Chi; Zuying Zhou; Ling Wang; Li Yuan; Lin Zheng; Yong Huang

doi:10.1016/j.jpba.2024.116156

Herb-drug interactions: Quantitative analysis of levofloxacin absorption and transporter expression in the rat intestine following combined treatment with Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross

J Pharm Biomed Anal. 2024 Apr 16:245:116156. doi: 10.1016/j.jpba.2024.116156. Online ahead of print.

Authors

Yang Zhou¹, Mingyan Chi², Zuying Zhou¹, Ling Wang¹, Li Yuan¹, Lin Zheng³, Yong Huang⁴

Affiliations

¹ State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China.
² School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China; National Engineering Research Center of Miao's Medicines, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang 550004, China.
³ State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China. Electronic address: ZHENGL2020@126.com.
⁴ State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang 550004, China; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China. Electronic address: HUANGY2020@126.com.

PMID: 38636190
DOI: 10.1016/j.jpba.2024.116156

Abstract

Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, a traditional Chinese medicinal plant, is often used to treat various urologic disorders in China. P. capitata extracts (PCE) have been used in combination with levofloxacin (LVFX) to treat urinary tract infections (UTIs) for a long time. However, little is known about the absorption of LVFX and transporter expression in the intestine after combined treatment with PCE, restricting the development and utilization of PCE. In view of this, a UPLC-MS/MS method was established for the determination of LVFX in intestinal sac fluid samples and in situ intestinal circulation perfusate samples to explore the effect of PCE on the intestinal absorption characteristics of LVFX ex vivo and in vivo. To further evaluate the interaction between LVFX and PCE, western blotting, immunohistochemistry, and RT-qPCR were utilized to determine the expression levels of drug transporters (OATP1A2, P-gp, BCRP, and MRP2) involved in the intestinal absorption of LVFX after combined treatment with PCE. Using the everted intestinal sac model, the absorption rate constant (K_a) and cumulative drug absorption (Q) of LVFX in each intestinal segment were significantly lower in groups treated with PCE than in the control group. K_a at 2 h decreased most in the colon segment (from 0.088 to 0.016 µg/h·cm²), and Q at 2 h decreased most in the duodenum (from 213.29 to 33.92 µg). Using the intestinal circulation perfusion model, the K_a value and percentage absorption rate (A) of LVFX in the small intestine decreased significantly when PCE and LVFX were used in combination. These results showed that PCE had a strong inhibitory effect on the absorption of LVFX in the rat small intestine (ex vivo and in vivo intestinal segments). In addition, PCE increased the protein and mRNA expression levels of efflux transporters (P-gp, BCRP, and MRP2) and decreased the expression of the uptake transporter OATP1A2 significantly. The effects increased as the PCE concentration increased. These findings indicated that PCE changed the absorption characteristics of levofloxacin, possibly by affecting the expression of transporters in the small intestine. In addition to revealing a herb-drug interaction (HDI) between PCE and LVFX, these results provide a basis for further studies of their clinical efficacy and mechanism of action.

Keywords: Drug transporters; Herb–drug interactions; Levofloxacin; Persicaria capitata; UPLC-MS/MS.