Your browser doesn't support javascript.
loading
Metabolism and Excretion of [14C]Mobocertinib, a Selective Covalent Inhibitor of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations, in Healthy Male Subjects.
Chen, Hao; Shah, Abhi; Kato, Suguru; Griffin, Robert; Zhang, Steven; Pusalkar, Sandeepraj; Cohen, Lawrence; Li, Yuexian; Chowdhury, Swapan K; Zhu, Sean Xiaochun.
Afiliación
  • Chen H; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.).
  • Shah A; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.).
  • Kato S; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.).
  • Griffin R; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.).
  • Zhang S; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.).
  • Pusalkar S; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.).
  • Cohen L; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.).
  • Li Y; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.).
  • Chowdhury SK; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.).
  • Zhu SX; Drug Metabolism and Pharmacokinetics, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (H.C., A.S., S.K., R.G., S.P., L.C., Y.L., S.K.C., S.X.Z.); and Quantitative Clinical Pharmacology, Takeda Development Center Americas, Inc., Cambridge, Massachusetts (S.Z.) xiaochun.zhu@takeda.c
Drug Metab Dispos ; 52(10): 1115-1123, 2024 Sep 16.
Article en En | MEDLINE | ID: mdl-39038951
ABSTRACT
Mobocertinib (formerly known as TAK-788) is a targeted covalent tyrosine kinase inhibitor of epidermal growth factor receptor with exon 20 insertion mutations. This article describes the metabolism and excretion of mobocertinib in healthy male subjects after a single oral administration of [14C]mobocertinib. Mobocertinib-related materials were highly covalently bound to plasma proteins such as human serum albumin. The mean extraction recovery of total radioactivity was only 3.9% for six individual Hamilton pooled plasma samples. After extraction, mobocertinib was the most abundant component accounting for 7.7% of total extracted circulating radioactivity (TECRA) in the supernatant. Each of identified metabolites accounted for <10% of TECRA. Mobocertinib underwent extensive first-pass metabolism with the fraction of the dose absorbed estimated to be approximately 91.7%. Fecal excretion of mobocertinib metabolites was the major elimination route. Mobocertinib was mainly eliminated via oxidative metabolism with a fraction of approximately 88% metabolized by CYP3A4/5. The other minor elimination pathways included cysteine conjugation, metabolism by other cytochrome P450s, and renal excretion of unchanged mobocertinib. SIGNIFICANCE STATEMENT This article describes the metabolism and excretion of a targeted covalent inhibitor mobocertinib in humans after a single oral administration of [14C]mobocertinib. Mobocertinib was highly covalently bound to human plasma proteins. No metabolite accounted for >10% of total extracted circulating radioactivity in human plasma. Mobocertinib was mainly eliminated via CYP3A4/5 mediated oxidative metabolism followed by fecal excretion after approximately 91.7% of the dose was absorbed.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Proteínas Quinasas / Receptores ErbB Límite: Adult / Humans / Male / Middle aged Idioma: En Revista: Drug Metab Dispos Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Proteínas Quinasas / Receptores ErbB Límite: Adult / Humans / Male / Middle aged Idioma: En Revista: Drug Metab Dispos Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos