Apomorphine: bioavailability and effect on stereotyped cage climbing in mice

Area of Science:

• Pharmacology
• Drug Metabolism

Background:

• Apomorphine is a dopamine agonist with therapeutic potential.
• Understanding its pharmacokinetic profile is crucial for effective drug development.

Purpose of the Study:

• To determine the absolute bioavailability of apomorphine in mice.
• To investigate the impact of different administration routes on apomorphine plasma levels and its conjugates.
• To explore the extent of first-pass metabolism.

Main Methods:

• Mice received intravenous, intraperitoneal, or oral doses of apomorphine.
• Plasma levels of apomorphine and its conjugates were quantified using high-performance liquid chromatography after hydrolysis.
• Apomorphine-induced stereotypical cage climbing behavior was monitored.

Main Results:

• Absolute oral bioavailability of apomorphine was determined to be 4%.
• Plasma concentrations of apomorphine and its conjugates varied significantly across administration routes.
• Cage climbing experiments suggested an absolute bioavailability of 16% for apomorphine.

Conclusions:

• Extensive hepatic conjugation leads to a significant first-pass effect for orally administered apomorphine.
• The route of administration critically influences apomorphine's pharmacokinetic behavior and bioavailability.
• Further research is needed to fully elucidate apomorphine's metabolic pathways.