Rates of absorption for insufflation & maximum bioavailability versus dosage

[Vastness]

I haven't been able to find this information anywhere really but I am curious both for reasons of scientific curiousity and also practical considerations with minimising inflamation or damage to the nasal passages caused by intranasal administration of various substances.

Has it ever been measured over what period of time it would take for the majority of a substance to be absorbed by the nasal mucosa, after which any further absorption would have a negligible increase in effect? If it exists, I would be very interested to see a graph with "percentage of substance absorbed" plotted versus time. For example, at 5 minutes, 10% of the substance has been absorbed, at 10 minutes, 20%, etc, etc...

Taking cocaine as an example as one of the most (if not the most?) commonly insufflated substances, I have seen it quoted that there is a peak plasma concentration seen at around 10 minutes following insufflation, and another peak at 45 minutes (the second peak is theorised to actually be a result of some cocaine being swallowed in the drip and absorbed by the stomach/digestive system - this obviously complicates things slightly). However I am not certain if peak plasma concentration actually corresponds with the point at which any remaining absorption would have a negligible impact on effects.

I guess what I am actually asking is, on average, after what period of time following a single nasally administered dose of a substance, would there be a negligible decrease in overall bioavailability and/or subjective effects if the user were to completely irrigate their nasal passages afterwards to remove all traces of the administered substance remaining in the nasal cavity?


Additionally, to what extent dose the total administered dose affect the overal bioavailability? For example, I would assume that of a 20mg dose of a substance, a higher percentage of this substance would be absorbed into the bloodstream, than if the user were to administer a 100mg dose. Is this something that can be calculated or plotted on a graph (for example, "Dose" vs "Total maximum bioavailability")? I would presume also that the higher dosage would also affect the rate of absorption. In fact, perhaps a better question to ask would be, does anyone know, or has there ever been an effort made, to calculate the maximum rate of absorption of any given substance by the nasal mucosa, in, say, mg/minute?

 

[sekio]

Absorbtion rates would vary for the individual substances and would fall off exponentially.

People do measure absorbtion of drugs nasally, just like any other absorbtion study the numbers they want are Tmax (time to peak drug concentration) and AUC (area under curve, or total drug absorbed*time)

 

[Vastness]

Thanks for your response. Yeah, I understand this will differ from substance to substance, I guess I was just hoping for some measured figures for various commonly insufflated substances.

Since posting I have found this study, which somewhat answers my question: https://www.ncbi.nlm.nih.gov/pubmed/9917048

Of the cocaine absorbed, 47% was absorbed within the first 5 min, 70% within 10 min, and 90% within 15 min

There was also another measurement taken at 20 minutes, but for some reason this is not included in the summary of results. Perhaps because after 15 minutes the remaining 10% was absorbed at too slow a rate to bother noting? This was for 160mg dissolved in saline and administered via cotton wool, as far as I can tell, however, for local anaesthetic purposes... I am therefore not sure if it would be directly applicable to the more common method of administration of recreational drug users, which is to insufflate dry powder. Of course presumably with repeated dosing, any substance will begin to inhibit it's own absorption due to irritation of the nasal mucosa, cocaine specifically due to localised vasoconstriction also. I would imagine that there is basically no data on this though.

I won't bother quoting because I don't have any primary sources for this but I have read on Ketamine's wikipedia that "the majority" of an insufflated dose is absorbed between 5 and 15 minutes, which is a wider range than I would like but I guess is within a similar range as cocaine. Why is this? Are the molecules a similar size, water solubility, or what? Assuming that a substance CAN be administered in this way, what factors affect rate of absorption?