Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine

Molecules

Tae Hwan Kim¹  Jürgen B. Bulitta¹  Sarah Kim¹  Seok Won Jeong²  Eunsook Ma²  Sang Hoon Joo²  Kwon-Yeon Weon²  Da Young Lee²  Soyoung Shin³  Gi-Young Park⁴  Dong Rak Kwon⁴  Beom Soo Shin⁵  Sun Dong Yoo⁵ 

[1] Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA;College of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, Korea;College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 54538, Korea;Department of Rehabilitation Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea;School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Korea;

关键词: herbal medicine;    drug-drug interaction;    pharmacokinetics;    gemcitabine;    erlotinib;    Hyangsayukgunja-tang;    population pharmacokinetic modeling;   

DOI  :  10.3390/molecules22091515

来源: DOAJ

【 摘 要 】

Gemcitabine and erlotinib are the chemotherapeutic agents used in the treatment of various cancers and their combination is being accepted as a first-line treatment of advanced pancreatic cancer. Hyangsayukgunja-tang (HYT) is a traditional oriental medicine used in various digestive disorders and potentially helpful to treat gastrointestinal adverse effects related to chemotherapy. The present study was aimed to evaluate the effect of HYT on the pharmacokinetics of gemcitabine and erlotinib given simultaneously in rats. Rats were pretreated with HYT at an oral dose of 1200 mg/kg/day once daily for a single day or 14 consecutive days. Immediately after pretreatment with HYT, gemcitabine and erlotinib were administered by intravenous injection (10 mg/kg) and oral administration (20 mg/kg), respectively. The effects of HYT on pharmacokinetics of the two drugs were estimated by non-compartmental analysis and pharmacokinetic modeling. The pharmacokinetics of gemcitabine and erlotinib were not altered by single dose HYT pretreatment. However, the plasma levels of OSI-420 and OSI-413, active metabolites of erlotinib, were significantly decreased in the multiple dose HYT pretreatment group. The pharmacokinetic model estimated increased systemic clearances of OSI-420 and OSI-413 by multiple doses of HYT. These data suggest that HYT may affect the elimination of OSI-420 and OSI-413.

【 授权许可】

Unknown