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
| Autor: | Teresa Fuller, Claire Ambery, Adam Hughes, Adrian Pereira, Graeme Young, Aili L. Lazaar, David Ramsay, Peter T. Daley-Yates, Frans van den Berg |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male microtracer chiral inversion Cmax Pharmaceutical Science Administration Oral Biological Availability Original Manuscript Urine Pharmacology Quinolones 030226 pharmacology & pharmacy Excretion 03 medical and health sciences Feces 0302 clinical medicine Pharmacokinetics Oral administration Administration Inhalation Medicine Humans Pharmacology (medical) Carbon Radioisotopes batefenterol Cross-Over Studies business.industry Correction Articles Middle Aged Healthy Volunteers Pharmacokinetics: Excretion Bioavailability Bronchodilator Agents 030220 oncology & carcinogenesis Concomitant Administration Intravenous Carbamates business pharmacokinetics |
| Zdroj: | Clinical Pharmacology in Drug Development Clin Pharmacol Drug Dev |
| ISSN: | 2160-7648 2160-763X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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