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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-09-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/22/9/1515 |
| _version_ | 1818152152943558656 |
|---|---|
| author | Tae Hwan Kim Soyoung Shin Sarah Kim Jürgen B. Bulitta Kwon-Yeon Weon Sang Hoon Joo Eunsook Ma Sun Dong Yoo Gi-Young Park Dong Rak Kwon Seok Won Jeong Da Young Lee Beom Soo Shin |
| author_facet | Tae Hwan Kim Soyoung Shin Sarah Kim Jürgen B. Bulitta Kwon-Yeon Weon Sang Hoon Joo Eunsook Ma Sun Dong Yoo Gi-Young Park Dong Rak Kwon Seok Won Jeong Da Young Lee Beom Soo Shin |
| author_sort | Tae Hwan Kim |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T13:50:11Z |
| format | Article |
| id | doaj.art-b643a450846141adb124b5d425bca925 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T13:50:11Z |
| publishDate | 2017-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b643a450846141adb124b5d425bca9252022-12-22T01:04:18ZengMDPI AGMolecules1420-30492017-09-01229151510.3390/molecules22091515molecules22091515Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal MedicineTae Hwan Kim0Soyoung Shin1Sarah Kim2Jürgen B. Bulitta3Kwon-Yeon Weon4Sang Hoon Joo5Eunsook Ma6Sun Dong Yoo7Gi-Young Park8Dong Rak Kwon9Seok Won Jeong10Da Young Lee11Beom Soo Shin12Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USACollege of Pharmacy, Wonkwang University, Iksan, Jeonbuk 54538, KoreaCenter for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USACenter for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USACollege of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, KoreaCollege of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, KoreaCollege of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, KoreaDepartment of Rehabilitation Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaDepartment of Rehabilitation Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, KoreaCollege of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, KoreaCollege of Pharmacy, Catholic University of Daegu, 13-13 Hayang-ro, Hayang-eup, Gyeongsan-si, Gyeongbuk 38430, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, KoreaGemcitabine 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.https://www.mdpi.com/1420-3049/22/9/1515herbal medicinedrug-drug interactionpharmacokineticsgemcitabineerlotinibHyangsayukgunja-tangpopulation pharmacokinetic modeling |
| spellingShingle | Tae Hwan Kim Soyoung Shin Sarah Kim Jürgen B. Bulitta Kwon-Yeon Weon Sang Hoon Joo Eunsook Ma Sun Dong Yoo Gi-Young Park Dong Rak Kwon Seok Won Jeong Da Young Lee Beom Soo Shin Alterations in Pharmacokinetics of Gemcitabine and Erlotinib by Concurrent Administration of Hyangsayukgunja-Tang, a Gastroprotective Herbal Medicine Molecules herbal medicine drug-drug interaction pharmacokinetics gemcitabine erlotinib Hyangsayukgunja-tang population pharmacokinetic modeling |
| 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 | herbal medicine drug-drug interaction pharmacokinetics gemcitabine erlotinib Hyangsayukgunja-tang population pharmacokinetic modeling |
| url | https://www.mdpi.com/1420-3049/22/9/1515 |
| work_keys_str_mv | AT taehwankim alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT soyoungshin alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT sarahkim alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT jurgenbbulitta alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT kwonyeonweon alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT sanghoonjoo alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT eunsookma alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT sundongyoo alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT giyoungpark alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT dongrakkwon alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT seokwonjeong alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT dayounglee alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine AT beomsooshin alterationsinpharmacokineticsofgemcitabineanderlotinibbyconcurrentadministrationofhyangsayukgunjatangagastroprotectiveherbalmedicine |