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The study found that NNMT inhibitors "reduced intracellular 1-MNA, increased intracellular NAD+ and S-(5-adenosyl)-L-methionine (SAM), and suppressed lipogenesis." This metabolic improvement occurs within days of starting treatment, before any weight loss becomes measurable

Don't let the needle touch anything once the cap is off

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

treatment often starts with an aggressive loading dose of 1000 mcg injections several times a week before tapering to monthly or bimonthly shots once levels stabilize

Reference: Dimet-Wiley AL, Latham CM, Brightwell CR, Neelakantan H, Keeble AR, Thomas NT, Noehren H, Fry CS, Watowich SJ (2024)