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Kinetics and disposition of picumeterol in animals
1Glaxo Research and Development Ltd, Drug Metabolism Division, Ware, UK.
Xenobiotica; the Fate of Foreign Compounds in Biological Systems
|September 1, 1995
Summary
Picumeterol, a beta 2 receptor agonist, is absorbed via inhalation and rapidly eliminated after intravenous administration. Extensive metabolism occurs in rats and dogs, with primary excretion via urine.
Area of Science:
- Pharmacology
- Drug Metabolism
- Pharmacokinetics
Background:
- Picumeterol is a novel beta 2 receptor agonist.
- Understanding its pharmacokinetic profile is crucial for therapeutic development.
Purpose of the Study:
- To investigate the pharmacokinetics and disposition of picumeterol.
- To evaluate absorption, distribution, metabolism, and excretion (ADME) in preclinical models.
Main Methods:
- Administered picumeterol via inhalation, intravenous, and oral routes in rats and dogs.
- Utilized radiolabeled picumeterol (14C-picumeterol) for disposition studies.
- Analyzed plasma, urine, and bile for drug and metabolite concentrations.
Main Results:
- Picumeterol transferred across the lung after inhalation; rapid plasma elimination with half-lives of ~1h (rat) and ~2h (dog) post-IV.
- Extensive in vivo and in vitro metabolism (~95% rat, ~90% dog) via O-dealkylation and beta-oxidation.
- Low oral bioavailability due to extensive first-pass metabolism; primary excretion of metabolites in urine.
Conclusions:
- Picumeterol exhibits rapid elimination and extensive metabolism, suggesting potential for targeted delivery via inhalation.
- Metabolic pathways identified (O-dealkylation, beta-oxidation) are key to its disposition.
- Further studies are warranted to optimize dosing and delivery for clinical application.
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