AOD-9604 Dosage in Research: Doses, Routes, and Half-Life

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This page describes AOD-9604 dosage only as it appears in the research literature — what was given to which species, by which route, for how long. It is not a how-to, and it contains no recommended human dose. That matters here for a specific reason: the human studies did not show the weight loss they tested for, so there is no "effective dose" to point to ^[12]. Doses below are written as figures of record: a mouse study, a rabbit study, a human trial. The peptide clears the bloodstream very fast — its intravenous half-life (the time for blood levels to fall by half) is about 3 minutes in a pig model — and it breaks down from one end of the chain ^[6]. Treat everything here as a reading of published numbers, not guidance.

Doses studied, by species and route

Preclinical and clinical dosing of AOD-9604 spanned several routes. Foundational preclinical oral dosing used synthetic hGH 177-191 in obese (ob/ob) mice. A 14-day chronic intraperitoneal regimen was used in obese and beta3-AR knockout mice ^[1]. Early human Phase I work used single intravenous doses across roughly 25-400 mcg/kg in Metabolic Pharmaceuticals studies. The human Phase II obesity program used daily oral doses ranging from 0.25 mg up to 54 mg across studies, with a 24-week trial using 0.25 mg, 0.5 mg, and 1 mg/day ^[5]. In the rabbit osteoarthritis model, 0.25 mg per knee was injected weekly for 4-7 weeks by the intra-articular route.

These figures are reported strictly as studied amounts in named species by named routes — for example, "14-day chronic IP, obese mice" or "0.25 mg/knee weekly, rabbit OA, intra-articular." None of them is a human-use instruction.

Routes, half-life, and stability

Four routes appear in the literature: oral (the primary route in the human obesity program), intravenous (Phase I human and pig PK), intra-articular (the rabbit osteoarthritis model), and intraperitoneal or continuous infusion (preclinical mouse studies) ^[5][6].

The pharmacokinetics are short. The intact peptide is rapidly cleared, with an intravenous half-life of about 3 minutes in a pig model, degrading by sequential removal of amino acids from the N-terminus in a cascade fashion ^[6]. On stability, the molecule contains an intramolecular disulfide bridge and is relatively stable in lyophilised (freeze-dried) form, but in plasma it is rapidly degraded from the N-terminus by aminopeptidases. Formal long-term stability data under varied storage conditions has not been published in the primary clinical literature ^[6].

What the human program established

Roughly 900 participants were dosed across about six randomised, double-blind, placebo-controlled trials run by Metabolic Pharmaceuticals through the 2000s, with daily oral doses from 0.25 mg to 54 mg and durations from 7 days to 24 weeks ^[5]. Safety and tolerability were reported as indistinguishable from placebo and free of full-length-growth-hormone adverse effects ^[5].

The pivotal Phase IIb obesity trial did not demonstrate statistically significant weight loss versus placebo, and the obesity development program was discontinued around 2007 ^[12]. The compound was not approved for any indication. Because there is no approved use and no demonstrated efficacious dose in humans, this page does not — and cannot honestly — point to a human protocol. It reports only what was studied. For the dose-by-dose study context, see the AOD-9604 research page and the AOD-9604 references.