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The CYP3A inducer dexamethasone affects the pharmacokinetics of sunitinib by accelerating its metabolism in rats.
Lu, Guang-Rong; Wang, Rui-Zhen; Zhao, Xin-Yu; Xu, Jun-Er; Huang, Cheng-Ke; Sun, Wei; Chen, Rui-Jie; Wang, Zhe.
Afiliación
  • Lu GR; Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • Wang RZ; Department of Pharmacy, Wenzhou People's Hospital, Wenzhou, Zhejiang, China.
  • Zhao XY; Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • Xu JE; Alberta Institute, Wenzhou Medical University, Zhejiang, China.
  • Huang CK; Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • Sun W; Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • Chen RJ; Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • Wang Z; Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: wangzhephar@163.com.
Chem Biol Interact ; 403: 111228, 2024 Nov 01.
Article en En | MEDLINE | ID: mdl-39244184
ABSTRACT
Sunitinib, a novel anti-tumor small molecule targeting VEGFR, is prescribed for advanced RCC and GISTs. Sunitinib is primarily metabolized by the CYP3A enzyme. It is well-known that dexamethasone serves as a potent inducer of this enzyme system. Nonetheless, the effect of dexamethasone on sunitinib metabolism remains unclear. This study examined the effect of dexamethasone on the pharmacokinetics of sunitinib and its metabolite N-desethyl sunitinib in rats. The plasma levels of both compounds were measured using UHPLC-MS/MS. Pharmacokinetic parameters and metabolite ratio values were calculated. Compare to control group, the low-dose dexamethasone group and high-dose dexamethasone group decreased the AUC(0-t) values of sunitinib by 47 % and 45 %, respectively. Meanwhile, the AUC(0-t) values of N-desethyl sunitinib were increased by 2.2-fold and 2.4-fold in low-dose dexamethasone group and high-dose dexamethasone group, respectively. The CL values for sunitinib were both approximately 45 % higher in the two dexamethasone groups. Remarkably, metabolite ratio values increased over 5-fold in both low-dose dexamethasone group and high-dose dexamethasone group, indicating a significant enhancement of sunitinib metabolism by dexamethasone. Moreover, the total levels of sunitinib and its metabolite are also significantly increased. The impact of interactions on sunitinib metabolism, as observed with CYP3A inducers such as dexamethasone, is a crucial consideration for clinical practice. To optimize the dosage and prevent adverse drug events, therapeutic drug monitoring can be employed to avoid the toxicity from such interactions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirroles / Dexametasona / Ratas Sprague-Dawley / Citocromo P-450 CYP3A / Sunitinib / Indoles Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirroles / Dexametasona / Ratas Sprague-Dawley / Citocromo P-450 CYP3A / Sunitinib / Indoles Límite: Animals Idioma: En Revista: Chem Biol Interact Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda