Oxandrolone via Troche to Bypass First Pass Metabolism. Effective?

[tareload]

I’d be interested in hearing others experience using oxandrolone troches instead of oral delivery (capsules) to bypass first-pass metabolism and reduce liver toxicity and lower minimum effective dose. Since oxandrolone has excellent oral bioavailability (97-98%) and is actually metabolized partially by kidneys (haven’t looked at the original studies to support this assertion), I have a hard time believing that sublingual/buccal administration is going to do much to lower liver damage for same dosage (i,e, you end up swallowing most of the troche as it dissolves?). I’ve pulled 10-15 studies and most seem to show similar pharmacokinetics for oral and sublingual administration of drugs that are metabolized similarly (ie CYP 3A4).

Here’s an example with DHEA troche, similar result to oral administration (pill):
Novel dehydroepiandrosterone troche supplementation improves the serum androgen profile of women undergoing in vitro fertilization

A few thoughts:
Seems like oxandrolone’s reputation for “mildness” is related to dosage and individual’s genetic response. 50-100 mg/day of oxandrolone probably ain’t gonna give the same result as 20 mg/day so just wanted to daylight the obvious. Caffeine or other CYP450 modulation also to be considered. Thanks for sharing your experiences on dosage experience Nelson. I don’t think anyone is doing histology on the kidneys while trial participants are running oxandrolone but perhaps that’s another place to look.

Treatment with oxandrolone and the durability of effects in older men

I was just genuinely curious why oxandrolone is dispensed from legitimate pharmacies via troche when its oral (delivery via digestive system) bioavailability is so high. Seems like a hammer in search of a nail. What am I missing? Hence I thought about avoiding liver damage. But, just because the drug doesn’t get delivered to liver/circulation via portal system doesn’t mean it can’t come back to the liver/kidney via serum for additional metabolism. Seems to me a troche’s strength is to get molecules (which have low oral bioavailability) into circulation by increasing bioavailability (avoid digestive system) and not to minimize end-organ metabolism damage. I can’t find an example of the latter in the literature.

Now, with regard to the delivery systems, would be an interesting experiment to test these different delivery modes on CMP/SHBG, lipids (hepatic lipase etc.). Appears to be a challenge for some to keep serum T levels reasonable (even with exogenous T usage) while also running oxandrolone since SHBG heads toward zero:

Low sex hormone-binding globulin and testosterone levels in association with erectile dysfunction among human immunodeficiency virus-infected men receiving testosterone and oxandrolone.

On second thought, I probably need to correct myself. If you can get drug into systemic circulation (while avoiding first pass) where it presents at reduced systemic serum concentration (vs concentration upon introduction into portal vein) and metabolic clearance typically first order function of serum concentration, I can see where this concept has legs although effect may be quite minimal with highly bioavailable oxandrolone. Especially if most of the metabolic clearance is done in kidneys anyway. In short, dilution may be the solution.

Nice demonstration of the measurements and procedure you’d leverage clinically to study this with oral vs sublingual / rectal approaches:
Moment Analysis of Intestinal First-Pass Metabolism by Portal–Systemic Concentration Difference in Single Conscious Rat Using 5′-Deoxy-5-Fluorouridine and 5-Fluorouracil as Model Drug System

Thanks for sharing any experiences.

 

[CoastWatcher]

I’d be interested in hearing others experience using oxandrolone troches instead of oral delivery (capsules) to bypass first-pass metabolism and reduce liver toxicity and lower minimum effective dose. Since oxandrolone has excellent oral bioavailability (97-98%) and is actually metabolized partially by kidneys (haven’t looked at the original studies to support this assertion), I have a hard time believing that sublingual/buccal administration is going to do much to lower liver damage for same dosage (i,e, you end up swallowing most of the troche as it dissolves?). I’ve pulled 10-15 studies and most seem to show similar pharmacokinetics for oral and sublingual administration of drugs that are metabolized similarly (ie CYP 3A4).

Here’s an example with DHEA troche, similar result to oral administration (pill):
Novel dehydroepiandrosterone troche supplementation improves the serum androgen profile of women undergoing in vitro fertilization

A few thoughts:
Seems like oxandrolone’s reputation for “mildness” is related to dosage and individual’s genetic response. 50-100 mg/day of oxandrolone probably ain’t gonna give the same result as 20 mg/day so just wanted to daylight the obvious. Caffeine or other CYP450 modulation also to be considered. Thanks for sharing your experiences on dosage experience Nelson. I don’t think anyone is doing histology on the kidneys while trial participants are running oxandrolone but perhaps that’s another place to look.

Treatment with oxandrolone and the durability of effects in older men

I was just genuinely curious why oxandrolone is dispensed from legitimate pharmacies via troche when its oral (delivery via digestive system) bioavailability is so high. Seems like a hammer in search of a nail. What am I missing? Hence I thought about avoiding liver damage. But, just because the drug doesn’t get delivered to liver/circulation via portal system doesn’t mean it can’t come back to the liver/kidney via serum for additional metabolism. Seems to me a troche’s strength is to get molecules (which have low oral bioavailability) into circulation by increasing bioavailability (avoid digestive system) and not to minimize end-organ metabolism damage. I can’t find an example of the latter in the literature.

Now, with regard to the delivery systems, would be an interesting experiment to test these different delivery modes on CMP/SHBG, lipids (hepatic lipase etc.). Appears to be a challenge for some to keep serum T levels reasonable (even with exogenous T usage) while also running oxandrolone since SHBG heads toward zero:

Low sex hormone-binding globulin and testosterone levels in association with erectile dysfunction among human immunodeficiency virus-infected men receiving testosterone and oxandrolone.

On second thought, I probably need to correct myself. If you can get drug into systemic circulation (while avoiding first pass) where it presents at reduced systemic serum concentration (vs concentration upon introduction into portal vein) and metabolic clearance typically first order function of serum concentration, I can see where this concept has legs although effect may be quite minimal with highly bioavailable oxandrolone. Especially if most of the metabolic clearance is done in kidneys anyway. In short, dilution may be the solution.

Nice demonstration of the measurements and procedure you’d leverage clinically to study this with oral vs sublingual / rectal approaches:
Moment Analysis of Intestinal First-Pass Metabolism by Portal–Systemic Concentration Difference in Single Conscious Rat Using 5′-Deoxy-5-Fluorouridine and 5-Fluorouracil as Model Drug System

Thanks for sharing any experiences.

Thanks for posting an interesting question.

 

[sammmy]

I am currently taking Oxandrolone oral capsules and was not able to find any pharmacokinetic studies except one very old one that is constantly cited by other papers: Oxandrolone disposition and metabolism in man.
I have access only to the abstract from which it seems that Oxandrolone was dissolved in "ethanolic solution". This is not the way it is taken normally so I doubt this pharmacokinetics is at all applicable, although it is constantly cited.

 

[Rock H. Johnson]

Full paper:
https://sci-hub.tw/10.1002/cpt1973145862

 

[Nelson Vergel]

I have a hard time believing that sublingual/buccal administration is going to do much to lower liver damage for same dosage

Oxandrolone causes mild ALT and AST elevations but no GGT or bilirubin. So does resistance exercise. Oxandrolone is not liver toxic. But it causes a sharp drop in good cholesterol that is reversible after you stop the drug.

 

[tareload]

Oxandrolone causes mild ALT and AST elevations but no GGT or bilirubin. So does resistance exercise. Oxandrolone is not liver toxic. But it causes a sharp drop in good cholesterol that is reversible after you stop the drug.

Thanks you for the comments. I should have written "dysfunctional liver metabolism" rather than "liver damage" in my comments. The former indicates the liver is not behaving like it would normally, whereas the latter indicates physical damage being done to the liver.

Whether troche or capsule, I can report extreme nonlinear dose response for oxandrolone on HDL. Whether I took average dose of 7.5 mg per day or 50 mg per day, HDL was still crushed by 50-70%. Curious that Lp(a) was extremely low while taking oxandrolone. On the whole, I am not comfortable with the net/net to confidently take oxandrolone given whatever long-term implications the above data indicate.

 

[sammmy]

That's correct, the HDL reduction is almost independent of the oxandrolone dose.

I took 15mg/day and my HDL decreased by 30mg/dL = 50% at the 19th and 28th day. It remains constant after the initial reduction though.

The liver enzymes got progressively worse and AST got out of normal range at the 28th day. Probably would get even worse if I continued.