Herb-Drug Interaction Between Sailuotong and Pitavastatin: A Systematic Pharmaco...

연구 요약

Herb-Drug Interaction Between Sailuotong and Pitavastatin: A Systematic Pharmacokinetic Investigation and Mechanism Analysis.

Drug design, development and therapy 학술지에 발표된 이 연구는 Zhang Y, Yi H, Yang H 외 연구팀이 수행하였습니다.

이 연구는 'Herb-Drug Interaction Between Sailuotong and Pitavastatin: A Systematic Pharmacokinetic Investigation and Mechanism Analysis.'에 대한 과학적 분석을 제공합니다.

핵심 내용

PROPOSE: Sailuotong (SLT), a standardized Chinese herbal preparation for vascular dementia (VaD), is frequently co-administered with pitavastatin (PIV). Potential herb-drug interactions (HDIs) between these agents remain uncharacterized. Given the high likelihood of using this combination to treat VaD, this study aims to systematically evaluate the effects of SLT on PIV's pharmacokinetics and elucidate underlying mechanisms. METHODS: Rats received single or repeated doses of SLT followed by oral or intravenous PIV. Plasma and hepatic PIV concentrations were quantified via LC-MS/MS. Biliary excretion and enterohepatic circulation interruption models assessed elimination pathways. The expression of hepatic and intestinal transporters was analyzed by RT-PCR and Western blot. Transporter functionality was validated using MDR1 substrates (digoxin and betrixaban). RESULTS: Single-dose SLT increased PIV's Cmax and AUC0-9h by approximately 23.30% and 15.70%, respectively. Repeated SLT administration significantly decreased PIV's AUC by 32.90%, and reduced its hepatic accumulation by 68.96%. Intravenous studies revealed that SLT primarily affected the later exposure phases. Multiple doses of SLT decreased PIV's total biliary excretion by 33.10%. Mechanistically, SLT significantly induced the expression of MDR1 mRNA and proteins in the intestine and liver, and MRP2 in the liver. Additionally, SLT significantly decreased the exposure levels of digoxin and betrixaban, with betrixaban's Cmax and AUC remarkably reduced by 86.44% and 79.74%, respectively. CONCLUSION: Combining SLT and PIV can lead to HDIs, with multiple doses of SLT significantly reducing the plasma and hepatic exposure of PIV in rats. The primary mechanism appears to be the induction of the intestinal efflux transporter MDR1, resulting in decreased bioavailability of PIV.

일반인을 위한 해석

구체적인 실천 사항은 담당 의사 또는 약사와 상담하시기 바랍니다.

실천 사항

• 현재 복용 중인 약물이나 영양제에 대해 궁금한 점이 있다면 담당 의사 또는 약사와 상담하시기 바랍니다
• 약물이나 영양제의 용법·용량을 임의로 변경하지 마세요
• 이상 반응이 나타나면 즉시 전문가에게 문의하세요

의사/약사의 전문적 판단을 대체하지 않습니다 (PMID: 40859972)

📄 [전문 보기 (Markdown)](fulltext/40859972-herb-drug-interaction-between-sailuotong-and-pitavastatin-a-.md)