r0entgen

3 hours ago, BurnieBurns said:

The 500 Dalton Rule is NOT absolute. Conventional topical dutasteride WILL go systemic to a small degree (albeit less than finasteride). I along with many others have still had side effects from this.

For context Ketoconazole is 531.431 Daltons and is applied topically all the time.

Formulations like Xyon or Farmacia Parati are designed to enhance the penetration to the dermis level over a timed release and get stuck there resulting in incredibly low amount going systemic.

Yeah but ketoconazole is usually applied topically to treat fungal infections, which occurs superficially on the outer layer of skin (epidermis)…

So I am trying to make sense on why so many people feel topical dutasteride will be more effective and have less side effects, but I cannot seem to understand it from a scientific standpoint. I am hoping someone can explain. 
 

So the thought behind the reason topical dutasteride will have less side effects is due to its high molecular weight (greater than 500 g/mol). So according to the 500 Dalton rule (https://pubmed.ncbi.nlm.nih.gov/10839713/),dutasteride will not penetrate the corneal layer, which is the outer layer of the epidermis. This part makes sense as to why topical dutasteride won’t go systemic. 
 

The part I don’t understand is how does this make topical dutasteride effective when the hair follicle is in the dermal papilla layer (which is in the dermis—the layer deeper and under the epidermis)? If it cannot penetrate beyond the corneal layer, how is it able to have its effect on the follicle?