An innovative phase I study in healthy subjects to determine the mass balance, elimination, metabolism, and absolute bioavailability of mitapivat.

ABSTRACT: Mitapivat, a first-in-class, oral, small-molecule, allosteric activator of the red blood cell-specific form of pyruvate kinase (PKR), was approved for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency. In this phase I mass balance study in healthy males, we administered a single ~120 mg oral dose of [¹⁴ C]mitapivat and a concomitant intravenous ~0.1 mg microdose of [¹³ C₆ ]mitapivat. We determined (1) the routes of total radioactivity excretion, including the mass balance of total radioactivity in urine and feces; (2) the pharmacokinetics of mitapivat and [¹³ C₆ ]mitapivat in plasma and total radioactivity in whole blood and plasma; (3) the absolute oral bioavailability of mitapivat; and (4) the metabolit

SUBMITTER: Prakash C 

PROVIDER: S-EPMC10582659 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature