Absolute Bioavailability of Vemurafenib in Patients With BRAF Mutation-Positive Malignancies.

Vemurafenib is a BRAF kinase inhibitor indicated for the treatment of patients with BRAF mutation-positive unresectable or metastatic melanoma and Erdheim-Chester disease. This phase 1, open-label, single-arm study was designed to estimate absolute bioavailability of oral vemurafenib at steady state and to characterize the pharmacokinetics of a single intravenous microdose of C-labeled vemurafenib in patients with BRAF mutation-positive malignancies. Patients received oral vemurafenib 960 mg twice daily on days 1 through 28, with a single intravenous infusion of C-labeled vemurafenib solution (3 mL, corresponding to a radioactive dose of 18.

Pediatric Safety of Polysorbates in Drug Formulations.

Polysorbates 20 and 80 are the most frequently used excipients in biotherapeutics, the safety data for which have been well documented in adults. The polysorbate content in therapeutic formulations that are administered to children, however, has been less clearly regulated or defined with regard to safety. In pediatric patients, excessive amounts of polysorbate in biotherapeutics have been linked to hypersensitivity and other toxicity-related effects.

If Euhydric and Isotonic Do Not Work, What Are Acceptable pH and Osmolality for Parenteral Drug Dosage Forms?

Parenteral products should aim toward being isotonic and euhydric (physiological pH). Yet, due to other considerations, this goal is often not reasonable or doable. There are no clear allowable ranges related to pH and osmolality, and thus, the objective of this review was to provide a better understanding of acceptable formulation pH, buffer strength, and osmolality taking into account the administration route (i.