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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wang H, Zhou C, Su Y, Gou K, Geng X, Qiu X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	itraconazole voriconazole ripretinib uplc-ms/ms pharmacokinetics beagle dog Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6b769a6e1bd24998aae7c5edd036179c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6b769a6e1bd24998aae7c5edd036179c
record_format	dspace
spelling	oai:doaj.org-article:6b769a6e1bd24998aae7c5edd036179c2021-11-30T18:50:36ZThe Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique1177-8881https://doaj.org/article/6b769a6e1bd24998aae7c5edd036179c2021-11-01T00:00:00Zhttps://www.dovepress.com/the-pharmacokinetic-effect-of-itraconazole-and-voriconazole-on-ripreti-peer-reviewed-fulltext-article-DDDThttps://doaj.org/toc/1177-8881Hui-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 dogWang HZhou CSu YGou KGeng XQiu XDove Medical Pressarticleitraconazolevoriconazoleripretinibuplc-ms/mspharmacokineticsbeagle dogTherapeutics. PharmacologyRM1-950ENDrug Design, Development and Therapy, Vol Volume 15, Pp 4865-4873 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	itraconazole voriconazole ripretinib uplc-ms/ms pharmacokinetics beagle dog Therapeutics. Pharmacology RM1-950
spellingShingle	itraconazole voriconazole ripretinib uplc-ms/ms pharmacokinetics beagle dog Therapeutics. Pharmacology RM1-950 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
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
format	article
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
title	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_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_sort	pharmacokinetic effect of itraconazole and voriconazole on ripretinib in beagle dogs by uplc-ms/ms technique
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/6b769a6e1bd24998aae7c5edd036179c
work_keys_str_mv	AT wangh thepharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT zhouc thepharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT suy thepharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT gouk thepharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT gengx thepharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT qiux thepharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT wangh pharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT zhouc pharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT suy pharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT gouk pharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT gengx pharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique AT qiux pharmacokineticeffectofitraconazoleandvoriconazoleonripretinibinbeagledogsbyuplcmsmstechnique
_version_	1718406330146881536

The Pharmacokinetic Effect of Itraconazole and Voriconazole on Ripretinib in Beagle Dogs by UPLC-MS/MS Technique

Ejemplares similares