SLU-PP-332 Oral Bioavailability: Why We Stopped Selling the Capsule

1. Does oral SLU-PP-332 get absorbed?

No, according to the people who made it. In December 2025, Cyrielle Billon, Kevin Appourchaux, Isabelle Cote and Thomas Burris published a paper in the Journal of Pharmacology and Experimental Therapeutics introducing a compound called SLU-PP-915. The reason they had to build it is stated in the second sentence of their abstract:

“We previously developed an ERR pan-agonist, SLU-PP-332 (332), which improves aerobic performance in mice but lacks oral bioavailability.”

Three things make that sentence hard to argue with. Burris is also the senior author on the 2023 paper that first described SLU-PP-332, so this is the developing lab grading its own compound. The statement is not hedged. And they acted on it, spending the effort to design a chemically distinct molecule rather than reformulating the one they already had.

2. Why does swallowing a drug change whether it works?

Because a swallowed drug takes a longer route, and the body removes some of it along the way. A capsule has to dissolve, survive the contents of the gut, cross the gut wall, and then travel through the liver before it reaches general circulation. The liver is where most drug-clearing enzymes live, and it can strip out the majority of a dose on that first pass. Pharmacologists call this first-pass metabolism, and it is the single most common reason a compound that works in a dish fails in a pill.

An injection skips all of it. The drug enters the bloodstream and reaches the liver as part of normal circulation rather than as a concentrated first pass. This is why route of administration is not a packaging preference. For some molecules it decides whether the drug is a drug at all.

3. What did human liver tissue do to it?

It took the molecule apart into nine pieces. In 2026, Tristan Moller, Oliver Krug and Mario Thevis at the German Sport University Cologne ran SLU-PP-332 through human liver S9 fraction and human liver microsomes, which are laboratory preparations of the enzyme systems that clear drugs. They identified nine metabolites: six phase-one transformations and three phase-two conjugates.

Two cautions on how to read that. It is a laboratory study, not a measurement taken in a person, so it tells you human liver enzymes engage this molecule readily rather than telling you what fraction of a capsule survives. And their reason for running it was anti-doping surveillance, not consumer safety. They built the assay because they expect athletes to use these compounds, and they say so.

4. Then why did the mouse results look so good?

Because the mice were injected. The 2023 paper in ACS Chemical Biology that introduced SLU-PP-332 reported real findings: mice given the compound ran farther, gained type IIa oxidative muscle fibers, and switched on the gene program muscle runs during aerobic exercise. A 2024 follow-up in obese mice showed higher energy expenditure, more fat oxidation, less fat mass and better insulin sensitivity.

None of that is in dispute, and none of it was delivered by mouth. The biology is real and the delivery is the problem. Those two facts sit together comfortably, which is exactly why the compound kept selling.

5. What is SLU-PP-915, and does it change the answer?

SLU-PP-915 is the orally active compound the same lab built after SLU-PP-332, and it is the clearest evidence that the oral problem is real. In the 2025 paper, SLU-PP-915 matched SLU-PP-332 on exercise performance when both were injected, and held comparable efficacy when given by mouth once systemic exposure was accounted for.

The takeaway from that table is narrow and worth stating plainly. SLU-PP-915 is not a fix for anyone taking SLU-PP-332 today. It has never been given to a human being either. It matters here only as proof that the lab closest to this chemistry treated the oral route as a real obstacle and solved it by starting over.

6. What did RxPepsDirect do about it?

We retired it. On September 20, 2026, RxPepsDirect removed both of its oral SLU-PP-332 products from the catalog: the 250 mcg capsule and the combination capsule pairing SLU-PP-332 with BAM-15. Our providers no longer prescribe either one.

The decision came down to one standard. Every product we offer has to make sense in the form a patient actually receives it. When the lab that invented SLU-PP-332 published that it does not survive oral delivery, an oral capsule no longer met that standard, so it came off the shelf. There was no safety issue behind the decision. It was about whether the product could do its job.

We kept the product pages up and updated them to explain the change, so anyone searching for SLU-PP-332 finds the evidence instead of a dead link. The full background is on the SLU-PP-332 guide.

7. Why do oral doses vary so wildly?

Because nobody can measure what is being absorbed, so the dose floats. Oral SLU-PP-332 products sold online range from micrograms to 50 milligram tablets and beyond, a spread of more than a hundredfold for the same molecule. There is no published human pharmacokinetic study to anchor any of them.

A dose range that wide is a signal in itself. When a compound has a known exposure, doses converge. When it does not, people escalate until they feel something, and what they feel cannot be separated from expectation without a placebo arm. No such arm exists for SLU-PP-332 in humans.

8. What should you ask a vendor still selling oral SLU-PP-332?

One question does most of the work: what is the oral bioavailability, and which published study measured it? If the answer is a percentage with no citation, that number was invented. A few more worth asking:

• Does a licensed prescriber review my order? A research-use-only vial sold without a prescription has nobody in the chain whose license is at risk.
• Which pharmacy compounds it, and is it named? An unnamed pharmacy is not a pharmacy you can look up.
• What happened when the 2025 paper came out? The evidence has been public since December 2025. A seller that takes evidence seriously should have an answer.

9. What if you already took it?

There is no safety concern with the SLU-PP-332 our providers prescribed, and nothing you need to do. The published finding is about absorption, not harm. If you have questions or would like to talk about other options, message your provider through the patient portal or bring it up at your next visit.

What fits next depends on your goal. Endurance, body composition and metabolic health each have different options, and your provider can walk through them with you. If anti-doping testing applies to you, treat SLU-PP-332 as high risk regardless of where you got it, because the detection methods already exist.

References

1. Billon C, Appourchaux K, Cote I, Burris TP. An orally active estrogen receptor-related receptor agonist, SLU-PP-915, enhances aerobic exercise capacity. J Pharmacol Exp Ther. 2025;393(1):103787. doi:10.1016/j.jpet.2025.103787
2. Moller T, Krug O, Thevis M. In vitro metabolism and analytical characterization of SLU-PP-332 and SLU-PP-915: novel pan-ERR agonists with doping potential. Rapid Commun Mass Spectrom. 2026;40(8):e70039. doi:10.1002/rcm.70039
3. Billon C, Sitaula S, Banerjee S, et al. Synthetic ERR alpha/beta/gamma agonist induces an ERR alpha-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol. 2023;18(4):756-771. doi:10.1021/acschembio.2c00720
4. Billon C, Schoepke E, Avdagic A, et al. A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther. 2024;388(2):232-240. doi:10.1124/jpet.123.001733