# AOD-9604 Dosage in Research: Doses Studied by Species and Route

> AOD-9604 dosage as studied in the literature — the doses, species, and routes used across mouse, rabbit, pig, and human studies. Research context only, no human dosing guidance.

Reported strictly as study data — never as a human protocol or recommendation.

## Read this first

This page describes how AOD-9604 dosage appears **in published studies** — in mice, rabbits, pigs, and human trials. It is research context, not instructions. There is no recommended human dose here, no "how to use," and no calculator, because AOD-9604 is investigational and not approved for any human use. Two facts shape everything below. First, in the human obesity program, oral doses spanning a wide range did not produce significant weight loss, so dose was not the limiting factor in a missing effect. Second, the peptide clears the bloodstream within minutes after an injection, which is why the human studies used an oral tablet rather than a shot. Doses are reported here exactly as the studies framed them: a quantity, a species, and a route — nothing more.

## Doses studied across species and routes

Across the literature, AOD-9604 (and its predecessor fragments) were administered as follows, reported strictly as study data:

- **Obese (ob/ob) mice, oral.** Foundational preclinical oral dosing in obese mice used synthetic hGH 177–191, the sequence that became AOD-9604.
- **Obese and beta3-AR knockout mice, intraperitoneal.** `14-day chronic` dosing by intraperitoneal injection in the beta-3 adrenergic receptor knockout study that dissected the chronic-versus-acute effect [1].
- **Human, intravenous (Phase I).** Single intravenous doses across roughly `25–400 mcg/kg` in early Metabolic Pharmaceuticals pharmacokinetic studies.
- **Human, oral (Phase II).** Daily oral doses ranging from `0.25 mg` up to `54 mg` across the obesity program; a 24-week trial used `0.25 mg`, `0.5 mg`, and `1 mg` per day [5].
- **Rabbit knee, intra-articular.** `0.25 mg` per knee, weekly for 4–7 weeks, with or without 6 mg hyaluronic acid, in the collagenase-induced osteoarthritis model [7].

None of these is a human-use recommendation. They are the conditions under which the compound was studied.

## Half-life, route, and stability

AOD-9604's intravenous half-life was about `3 minutes` in a pig pharmacokinetic model, with the intact peptide rapidly degraded from the N-terminus by aminopeptidases [6]. That very short systemic half-life is one reason the human obesity program built around an oral formulation, which demonstrated absorption in non-clinical work [6].

The molecule contains an intramolecular disulfide bridge and is relatively stable in lyophilized (freeze-dried) form, while in plasma it is cleared quickly. Formal long-term stability data under varied storage conditions has not been published in the primary clinical literature. The routes studied — oral, intravenous, intra-articular, and intraperitoneal — were chosen to answer specific scientific questions, not to define a use pattern.

## What the human dosing program actually showed

The most important thing the AOD-9604 dosing record shows is a non-result that dose could not fix. About 900 obese adults were studied across roughly six randomized, double-blind, placebo-controlled trials, 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 [5]. Yet the pivotal Phase IIb trial did not demonstrate statistically significant weight loss versus placebo, and the obesity development program was discontinued [14]. In other words: the program tested a broad dose range in humans and still did not establish efficacy. That is why this page describes doses as historical study parameters — and stops there.

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A forward-looking digest of the published science — bright on the mechanism, honest about the null result.