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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

Lipoate is an essential lipid modification that is required for catalysis by the -ketoglutarate dehydrogenase (OGDH) and pyruvate dehydrogenase (PDH) complexes

PMC 1171222

A clear demonstration was obtained that BPC 157 stimulated both the egr-1 gene (critical in proliferation, differentiation, and inflammation during cholestatic liver injury, cytokine and growth factor generation, and early extracellular matrix (collagen) formation) (Kim et al., 2006