Monday, November 1, 2010

Intranasal Availability of Opana

There was recently some discussion on Opiophile concerning the amount of bioavailable oxymorphone in crushed and insufflated tablets of the popular painkiller Opana ER.  (The most common method by which they are used for recreational purposes). Given oxymorphone's potentially lethal strength, it is important for users to keep tabs on how much they have consumed in a sitting.  Alas, a quick look at the available research reveals this may be a daunting task.

Our first exhibit would be Hussain, M. A. and Aungst, B. J. (1997), Intranasal absorption of oxymorphone. Journal of Pharmaceutical Sciences, 86: 975–976. doi: 10.1021/js960513x.  From the abstract:
The nasal bioavailability of oxymorphone HCl was determined. Rats were surgically prepared to isolate the nasal cavity, into which a solution of oxymorphone was administered. A reference group of rats was administered oxymorphone HCl intravenously. Plasma oxymorphone concentrations were determined by HPLC. Nasal absorption was rapid, nasal bioavailability was 43%, and the iv and nasal elimination profiles were similar. Oxymorphone HCl appears to have the solubility, potency, and absorption properties required for efficient nasal delivery, which is an alternative to injections.
I wonder how applicable information about surgically prepared rat nostrils is to the nostrils of a human user, or how the absorption of oxymorphone dissolved in saline solution compares to oxymorphone contained within ground-up pill powder. I suspect sniffing pills is less efficient than using saline, especially depending on how well the pills are crushed. The sniffer's technique introduces yet another variable: someone who is railing enormous lines will lose more to drip than someone who sniffs several small lines over a few minutes. Does the sniffer have a clear nose (at least at the start of the evening?)

Some of the pill will invariably be lost to the nose's natural immune systems: it will get covered in mucus and blown out just like other small foreign particles. The rest will either be absorbed into the bloodstream in the sinuses or carried via post-nasal drip to the stomach where we would see oral absorption rates. I do not know the percentage of any given pill which will fall into each category.

And then there's a factsheet on Opana ER on the National Institute of Health website.

Food Effect
After oral dosing with 40 mg of OPANA in healthy volunteers under fasting conditions or with a high-fat meal, the Cmax and AUC were increased by approximately 38% in fed subjects relative to fasted subjects. As a result, OPANA should be dosed at least one hour prior to or two hours after eating (see DOSAGE AND ADMINISTRATION).

Ethanol Effect
The effect of co-ingestion of alcohol with OPANA has not been evaluated. However, an in vivo study was performed to evaluate the effect of alcohol (40%, 20%, 4% and 0%) on the bioavailability of a single dose of 40 mg of OPANA ER (an extended-release formulation of oxymorphone) in healthy, fasted volunteers. Following concomitant administration of 240 mL of 40% ethanol the Cmax increased on average by 70% and up to 270% in individual subjects. Following the concomitant administration of 240 mL of 20% ethanol, the Cmax increased on average by 31% and up to 260% in individual subjects. In some individuals there was also a decrease in oxymorphone peak plasma concentrations. No effect on the release of oxymorphone from OPANA ER was noted in an in vitro alcohol interaction study. The mechanism of the in vivo interaction is unknown. Therefore, co-administration of oxymorphone and ethanol must be avoided.
While I'm not clear on how much fats or alcohol would influence the absorption of sniffed vs. oral Opana, I think it is reasonable to assume they might have at least some effect. Given all these variables, it would seem to me like 35% bioavailability would be a generous but not unreasonable estimate for intranasal Opana: higher levels might well be achieved under certain circumstances. I would also caution that this may vary a good bit based on any number of factors, and urge users to dose conservatively.

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