Pharmacokinetics Excretion and Mass Balance of 14C‐Batefenterol Following a Single Microtracer Intravenous Dose (Concomitant to an Inhaled Dose) or Oral Dose of Batefenterol in Healthy Men

摘要

Inhaled batefenterol is an investigational bifunctional molecule for the treatment of chronic obstructive pulmonary disease. The excretion balance and pharmacokinetics of batefenterol using [¹⁴C]‐radiolabeled drug administered orally and as intravenous (IV) infusion were assessed. In this 2‐period, open‐label study, 6 healthy male subjects received a single IV microtracer 1‐hour infusion of 4 μg [¹⁴C]‐batefenterol concomitant with inhaled nonradiolabeled batefenterol (1200 μg) followed by oral [¹⁴C]‐batefenterol (200 μg) in period 2 after a 14‐day washout. The primary end points included: the area under the concentration‐time curve from time zero to last time of quantifiable concentration (AUC0‐t); maximum observed concentration (Cmax); and time of occurrence of maximum observed concentration. Following IV administration, the geometric mean AUC0‐t of [¹⁴C]‐batefenterol was 121.9 pgEq • h/mL; maximum observed concentration and time of occurrence of maximum observed concentration were 92.7 pgEq/mL and 0.8 hours, respectively; absolute oral bioavailability was 0.012%. The mean AUC0‐t ratio indicated that [¹⁴C]‐batefenterol accounted for 85% of total circulating radioactivity in the plasma initially and declined rapidly following IV administration, but only ∼0.2% of total circulating radioactivity following oral administration. Cumulative mean recovery of total radioactive [¹⁴C]‐batefenterol in urine and feces was 6.31% and 77.6%, respectively. Overall, batefenterol exhibited low systemic bioavailability after inhaled and oral administration, and high fecal excretion and low urinary excretion following IV and oral administration.