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.

Anti-Abuse Mechanisms: TIMERx and OxyContin OP

In James Fogle's classic autobigraphical novel Drugstore Cowboy "blues" - Numorphan tablets containing 10mg of oxymorphone - are the Holy Grail of drugstore heists.  Containing few binders, these little azure beauties dissolved easily in water and made for the greatest (and not infrequently the last) rush of a junkie's shooting career.  In 1972 Numorphan tablets were pulled off pharmacy shelves, thanks to a rash of abuse-related deaths.

When Endo Pharmaceuticals decided to re-introduce oxymorphone to the market as Opana ER (Extended Release)^®, they employed TIMERx^®, a drug delivery system created by Penwest.  TIMERx tablets contain xanthan and locust bean gum. When swallowed, these components become a tight, thick gel which slowly releases oxymorphone into the patient's system.  This allows for steady, gradual dosing. It also makes it nearly impossible to use Opana ER intravenously.  When water is added to the powdered tablet, it becomes a needle-clogging gel which cannot be drawn up into a syringe or injected into a vein.  

Alas, an Opana ER tablet can be insufflated if it is powdered and kept dry: while there will be some gelling in the nose, plenty of oxymorphone will still reach the bloodstream through the sinuses.  And as the gel goes into the stomach via post-nasal drip, it will continue to have an effect.   While oxymorphone has a low oral bioavailability - roughly 90% is digested via "first pass" metabolism before entering the system - it is still twice as powerful milligram for milligram as a comparable dose of oxycodone. Snorted Opana has become very popular amongst many opiate afficionados for its long-lasting and euphoric high: quite a few of said afficionados have found themselves facing a harsh withdrawal when their Opana supply ran out. 

Purdue Pharma is still stinging from the debacle surrounding their "abuse-proof" oxycodone formulation, OxyContin^®.  Soon after its release users discovered that one could gain instant access to the active ingredient merely by crushing the pill.  Many took to shooting them up as a supposedly "safer" alternative to street heroin.  (In fact, IV usage of pills is extremely dangerous: talcosis, abscesses and other damage can result). Others snorted them to gain a slightly quicker rate of onset, despite the risks associated with that mode of usage.

The newest formulation of OxyContin, OxyContin OP, is a plastic matrix shot through with oxycodone.  The tablets are nearly impossible to crush and can only be shaved into flakes through hard work with a hose clamp, file or similar object.  They also gel when exposed to water: people who have tried snorting them report near-suffocation as their nose became clogged by a gluey substance with the texture of hot mozzarella cheese. As a result, OPs are not favored by those who use OxyContins recreationally. After their release the price of the original formulation rose to as much as $120 for an OC 80, while OP 80s could be had for $15 to $20. 

Unfortunately, OxyContin OPs have fallen out of favor with many chronic pain patients as well.  Many report the undigestible pills cause serious stomach upset.  Others claim they are considerably less effective for pain management. Many recreational users have put their minds to breaking the polymer matrix by microwaving and freezing, soaking it in Coca Cola,  using chemicals like acetone and MEK, placing them in epsom salts, or other equally ingenious methods. So far the results have been mixed: some users have injured themselves trying to IV the results of their home chemistry experiments, while others have turned to heroin as a cheaper, easily available substitute.