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Relative bioavailability of pediatric oral solution and tablet formulations of trametinib in adult patients with solid tumors
Author(s) -
Cox Donna S.,
Allred Alicia,
Zhou YanYan,
Infante Jeffrey R.,
Gordon Michael S.,
Bendell Johanna,
Jones Suzanne,
Burris Howard,
Orford Keith
Publication year - 2014
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.152
Subject(s) - trametinib , medicine , pharmacokinetics , crossover study , dabrafenib , pharmacology , mek inhibitor , bioavailability , adverse effect , palatability , gastroenterology , mapk/erk pathway , kinase , metastatic melanoma , cancer , vemurafenib , pathology , placebo , alternative medicine , biology , microbiology and biotechnology
Trametinib (Mekinist®) is a selective inhibitor of mitogen‐activated protein kinase kinase (MEK) approved in the United States as a single agent and in combination with dabrafenib (Tafinlar®) for treatment of patients with unresectable or metastatic melanoma with a positive BRAF V600E/V600K mutation for which a pediatric oral solution formulation is being developed. This open‐label, two‐period, two‐treatment, randomized, crossover study assessed the relative bioavailability of the trametinib pediatric oral solution compared to the tablet formulation after a single‐dose administration to adult patients with solid tumors. Primary pharmacokinetic endpoints derived from standard non‐compartmental methods were AUC 0–inf , AUC 0–t , and C max . As expected, C max was higher and T max earlier for the pediatric oral solution compared to the tablet formulation. Administration of the trametinib pediatric oral solution resulted in a 12%, 10%, 18%, and 71% higher AUC 0–inf , AUC 0–last , AUC 0–24 , and C max , respectively, as compared to the tablet formulation. Safety results were aligned with the known safety profile of trametinib. No serious or non‐serious adverse events resulted in study drug withdrawal. Palatability of the pediatric oral solution was evaluated and found to be acceptable to most adult patients, but may differ in the pediatric population.