The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique
Hui-jun Wang,1 Chun-yan Zhou,1 Yan-ding Su,1 Kai-feng Gou,1 Xiao-nan Geng,1 Xiang-jun Qiu1,2 1Department of Pharmacy, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People’s Republic of China; 2Functional Experiment Teaching Center, School of Basic Med...
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Dove Medical Press
2021-11-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/the-pharmacokinetic-effect-of-itraconazole-and-voriconazole-on-ripreti-peer-reviewed-fulltext-article-DDDT |
| _version_ | 1819038933526249472 |
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| author | Wang H Zhou C Su Y Gou K Geng X Qiu X |
| author_facet | Wang H Zhou C Su Y Gou K Geng X Qiu X |
| author_sort | Wang H |
| collection | DOAJ |
| description | Hui-jun Wang,1 Chun-yan Zhou,1 Yan-ding Su,1 Kai-feng Gou,1 Xiao-nan Geng,1 Xiang-jun Qiu1,2 1Department of Pharmacy, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People’s Republic of China; 2Functional Experiment Teaching Center, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People’s Republic of ChinaCorrespondence: Xiang-jun QiuFunctional Experiment Teaching Center, School of Basic Medical Sciences, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang, 471023, People’s Republic of ChinaTel +8613698882699Fax +86379-64830346Email lyxiangjun@126.comBackground: A new UPLC-MS/MS technique for the determination of ripretinib in beagle dog plasma was developed, and the pharmacokinetic effects of voriconazole and itraconazole on ripretinib in beagle dogs were studied.Methods: After extraction with ethyl acetate under alkaline conditions, ripretinib was detected using avapritinib as the internal standard (IS). The mobile phases were 0.1% formic acid-acetonitrile. The scanning method was multi-reaction monitoring using ESI+ source, and the ion pairs for ripretinib and IS were m/z 509.93→ 416.85 and 499.1→ 482.09, respectively. This animal experiment adopted a three period self-control experimental design. In the first period, ripretinib was orally administered to six beagle dogs at a dose of 5 mg/kg. In the second period, the same six beagle dogs were orally given itraconazole at a dose of 7 mg/kg, after 30 min, ripretinib was orally given. In the third period, voriconazole at a dose of 7 mg/kg was given orally, and then ripretinib was orally given. At different time points, the blood samples were collected. The concentration of ripretinib was detected, and the pharmacokinetic parameters of ripretinib were calculated.Results: Ripretinib had a good linear relationship in the range of 1– 1000 ng/mL. The precision, accuracy, recovery, matrix effect and stability met the requirements of the guiding principles. After erdafitinib combined with itraconazole, the Cmax and AUC0→t of ripretinib increased by 38.35% and 36.36%, respectively, and the t1/2 was prolonged to 7.53 h. After ripretinib combined with voriconazole, the Cmax and AUC0→t of ripretinib increased by 37.44% and 25.52%, respectively, and the t1/2 was prolonged to 7.33 h.Conclusion: A new and reliable UPLC-MS/MS technique was fully optimized and developed to detect the concentration of ripretinib in beagle dog plasma. Itraconazole and voriconazole could inhibit the metabolism of ripretinib in beagle dogs and increase the plasma exposure of ripretinib.Keywords: itraconazole, voriconazole, ripretinib, UPLC-MS/MS, pharmacokinetics, beagle dog |
| first_indexed | 2024-12-21T08:45:11Z |
| format | Article |
| id | doaj.art-6b769a6e1bd24998aae7c5edd036179c |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-21T08:45:11Z |
| publishDate | 2021-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-6b769a6e1bd24998aae7c5edd036179c2022-12-21T19:09:51ZengDove Medical PressDrug Design, Development and Therapy1177-88812021-11-01Volume 154865487371065The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS TechniqueWang HZhou CSu YGou KGeng XQiu XHui-jun Wang,1 Chun-yan Zhou,1 Yan-ding Su,1 Kai-feng Gou,1 Xiao-nan Geng,1 Xiang-jun Qiu1,2 1Department of Pharmacy, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People’s Republic of China; 2Functional Experiment Teaching Center, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People’s Republic of ChinaCorrespondence: Xiang-jun QiuFunctional Experiment Teaching Center, School of Basic Medical Sciences, Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang, 471023, People’s Republic of ChinaTel +8613698882699Fax +86379-64830346Email lyxiangjun@126.comBackground: A new UPLC-MS/MS technique for the determination of ripretinib in beagle dog plasma was developed, and the pharmacokinetic effects of voriconazole and itraconazole on ripretinib in beagle dogs were studied.Methods: After extraction with ethyl acetate under alkaline conditions, ripretinib was detected using avapritinib as the internal standard (IS). The mobile phases were 0.1% formic acid-acetonitrile. The scanning method was multi-reaction monitoring using ESI+ source, and the ion pairs for ripretinib and IS were m/z 509.93→ 416.85 and 499.1→ 482.09, respectively. This animal experiment adopted a three period self-control experimental design. In the first period, ripretinib was orally administered to six beagle dogs at a dose of 5 mg/kg. In the second period, the same six beagle dogs were orally given itraconazole at a dose of 7 mg/kg, after 30 min, ripretinib was orally given. In the third period, voriconazole at a dose of 7 mg/kg was given orally, and then ripretinib was orally given. At different time points, the blood samples were collected. The concentration of ripretinib was detected, and the pharmacokinetic parameters of ripretinib were calculated.Results: Ripretinib had a good linear relationship in the range of 1– 1000 ng/mL. The precision, accuracy, recovery, matrix effect and stability met the requirements of the guiding principles. After erdafitinib combined with itraconazole, the Cmax and AUC0→t of ripretinib increased by 38.35% and 36.36%, respectively, and the t1/2 was prolonged to 7.53 h. After ripretinib combined with voriconazole, the Cmax and AUC0→t of ripretinib increased by 37.44% and 25.52%, respectively, and the t1/2 was prolonged to 7.33 h.Conclusion: A new and reliable UPLC-MS/MS technique was fully optimized and developed to detect the concentration of ripretinib in beagle dog plasma. Itraconazole and voriconazole could inhibit the metabolism of ripretinib in beagle dogs and increase the plasma exposure of ripretinib.Keywords: itraconazole, voriconazole, ripretinib, UPLC-MS/MS, pharmacokinetics, beagle doghttps://www.dovepress.com/the-pharmacokinetic-effect-of-itraconazole-and-voriconazole-on-ripreti-peer-reviewed-fulltext-article-DDDTitraconazolevoriconazoleripretinibuplc-ms/mspharmacokineticsbeagle dog |
| spellingShingle | Wang H Zhou C Su Y Gou K Geng X Qiu X The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique Drug Design, Development and Therapy itraconazole voriconazole ripretinib uplc-ms/ms pharmacokinetics beagle dog |
| title | The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique |
| title_full | The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique |
| title_fullStr | The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique |
| title_full_unstemmed | The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique |
| title_short | The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique |
| title_sort | pharmacokinetic effect of itraconazole and voriconazole on ripretinib in beagle dogs by uplc ms ms technique |
| topic | itraconazole voriconazole ripretinib uplc-ms/ms pharmacokinetics beagle dog |
| url | https://www.dovepress.com/the-pharmacokinetic-effect-of-itraconazole-and-voriconazole-on-ripreti-peer-reviewed-fulltext-article-DDDT |
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