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Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine
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 po...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151743/ https://www.ncbi.nlm.nih.gov/pubmed/28891960 http://dx.doi.org/10.3390/molecules22091515 |
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author | Kim, Tae Hwan Shin, Soyoung Kim, Sarah Bulitta, Jürgen B. Weon, Kwon-Yeon Joo, Sang Hoon Ma, Eunsook Yoo, Sun Dong Park, Gi-Young Kwon, Dong Rak Jeong, Seok Won Lee, Da Young Shin, Beom Soo |
author_facet | Kim, Tae Hwan Shin, Soyoung Kim, Sarah Bulitta, Jürgen B. Weon, Kwon-Yeon Joo, Sang Hoon Ma, Eunsook Yoo, Sun Dong Park, Gi-Young Kwon, Dong Rak Jeong, Seok Won Lee, Da Young Shin, Beom Soo |
author_sort | Kim, Tae Hwan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6151743 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61517432018-11-13 Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine Kim, Tae Hwan Shin, Soyoung Kim, Sarah Bulitta, Jürgen B. Weon, Kwon-Yeon Joo, Sang Hoon Ma, Eunsook Yoo, Sun Dong Park, Gi-Young Kwon, Dong Rak Jeong, Seok Won Lee, Da Young Shin, Beom Soo Molecules Article 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. MDPI 2017-09-10 /pmc/articles/PMC6151743/ /pubmed/28891960 http://dx.doi.org/10.3390/molecules22091515 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kim, Tae Hwan Shin, Soyoung Kim, Sarah Bulitta, Jürgen B. Weon, Kwon-Yeon Joo, Sang Hoon Ma, Eunsook Yoo, Sun Dong Park, Gi-Young Kwon, Dong Rak Jeong, Seok Won Lee, Da Young Shin, Beom Soo Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine |
title | Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine |
title_full | Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine |
title_fullStr | Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine |
title_full_unstemmed | Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine |
title_short | Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine |
title_sort | alterations in pharmacokinetics of gemcitabine and erlotinib by concurrent administration of hyangsayukgunja-tang, a gastroprotective herbal medicine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151743/ https://www.ncbi.nlm.nih.gov/pubmed/28891960 http://dx.doi.org/10.3390/molecules22091515 |
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