AOD-9604 Pharmacokinetics & Metabolism Absorption & Distribution AOD-9604 exhibits unusual pharmacokinetic properties for a peptide, demonstrating activity via multiple administration routes in preclinical models: Oral bioavailability confirmed in pig and rodent studies, an uncommon characteristic for peptide compounds Rapid systemic distribution following intraperitoneal administration in mice (15-30 minutes) Following IV administration in pigs, AOD-9604 and degradation fragments appeared rapidly in plasma Oral administration showed slower kinetics but similar degradation product profiles Distribution studies using radiolabeled peptide (C-14-AOD9604) in rats revealed: Elevated concentrations in pineal body and thyroid tissues Distribution to all non-CNS tissues examined Minimal penetration of blood-brain barrier Tissue-specific accumulation patterns suggesting potential targeting mechanisms Metabolism & Elimination The metabolic fate of AOD-9604 involves rapid degradation through sequential N-terminal amino acid removal,: Plasma half-life of approximately 3 minutes following IV administration in pigs (compared to 21 minutes for full-length growth hormone) Sequential amino-terminal truncation represents the primary degradation pathway Principal metabolites identified in vivo include -2 amino acid and -3 amino acid fragments These truncated fragments retain some reduced in vitro anti-lipogenic activity A significant pharmacokinetic paradox exists: despite rapid plasma clearance (peptide undetectable at 56 minutes in spiked plasma studies), biological effects on body weight and fat metabolism persist for hours to days
In preclinical models, researchers observed that AOD9604 does not stimulate IGF-1 production or activate the growth hormone receptor, distinguishing it from full-length hGH
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For example, activation of the limbic and paralimbic systems, which are responsible for behavioral and emotional responses, are thought to contribute to distress signaling and complications of tinnitus, such as cognitive, mood, and sleep disorders, in some individuals
