A single‐dose mass balance and metabolite‐profiling study of vemurafenib in patients with metastatic melanoma

Vemurafenib, a selective inhibitor of oncogenic BRAF kinase carrying the V600 mutation, is approved for treatment of advanced BRAF mutation–positive melanoma. This study characterized mass balance, metabolism, rates/routes of elimination, and disposition of ¹⁴C‐labeled vemurafenib in patients with metastatic melanoma. Seven patients with metastatic BRAF‐mutated melanoma received unlabeled vemurafenib 960 mg twice daily for 14 days. On the morning of day 15, patients received ¹⁴C‐labeled vemurafenib 960 mg (maximum 2.56 MBq [69.2 μCi]). Thereafter, patients resumed unlabeled vemurafenib (960 mg twice daily). Blood, urine, and feces were collected for metabolism, pharmacokinetic, and dose recovery analysis. Within 18 days after dose, ~95% of ¹⁴C‐vemurafenib–related material was recovered from feces (94.1%) and urine (<1%). The parent compound was the predominant component (95%) in plasma. The mean plasma elimination half‐life of ¹⁴C‐vemurafenib–related material was 71.1 h. Each metabolite accounted for <0.5% and ≤6% of the total administered dose in urine and feces, respectively (0–96 h postdose). No new metabolites were detected. Vemurafenib was well‐tolerated. Excretion of vemurafenib via bile into feces is considered the predominant elimination route from plasma with minor renal elimination (<1%).

DOI: 10.1002/prp2.113

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