Autopsy report attributes death to MDMA

Just a brief note in follow up to a prior post on a death alleged to be from Ecstasy. The CourierMail is now reporting that the autopsy on Rosie Bebendorf attributes the death to MDMA.

But in establishing her death from MDMA (ecstasy) toxicity, an autopsy report received by Ms Bebendorf’s parents highlights two injection marks on her arm.
“The needle marks on the crook of the right elbow, which were fresh – a few hours old – could be the site where the drug was administered,” a government pathologist states.

Interesting. Very interesting indeed. Especially given all of the initial reporting characterized her as having “taken two Ecstasy tablets”. And then there is this odd note:

[Ms Bebendorf’s mother Gerry] believed it was “very unlikely (Rosie) injected herself” with the fatal dose of ecstasy, although she had known for some time that her daughter took speed intravenously.

So the autopsy concludes MDMA at fault. Presumably due to levels of MDMA judged to be high enough and no other drug levels seeming to be of threatening levels on the tox panels? Ahh, who knows. Still a frustrating lack of detail. The parents seem quite keen to go on record with the media quotes in a keep-others-off-MDMA mode, perhaps they would be kind enough to release the whole report.
The route of administration thing is interesting to contemplate. First because of the parents’ tone, as quoted, of poor little lamb daughter led astray by evil boyfriend. Those always ring hollow to me, as do the claims that it was the first time the kid ever did any drugs. Second because of the resulting questions about the pharmacokinetic profile when MDMA was injected rather than ingested. And then we get into possible nonMDMA contributors to the toxicity…

Thinking About Real World Fallout

So in case you missed it, since it occurred on a very bloggy timescale, our good blog friend DamnedGoodTechnician was outed at work. Leading to much unpleasantness with some people above her in the management chain at MassivePharma. DGT then decided to pull the blog.
This event led to much thinking on the risks of overly-personal or overly-detailed blogstylings here and there. Hit the posts and read through the comments if you want a full flavor.
Prof in Training (and here)
Prof-Like Substance
Odyssey
Dr. Isis’s Rules for Pseud Blogging
Ambivalent Academic
Now, as it turns out, DGT has returned to blogging. From appearances DGT’s job is safe, it is just a matter of damaged relationships with the bosses.
I hate to be the wet blanket but it is well worth thinking about.

Metabolism of MDMA via CYP2D6

See, now this is the problem with trying to make complex scientific points relatively simple. They never are. Biology and physiology are complicated and thus we end up minimizing or overlooking important aspects at times. Luckily in the blogosphere someone is usually all over it.
Abel Pharmboy responded to my recent post on a paper comparing MDMA pharmacokinetics between humans and one of the animal models which has generated the most specific and controversial data as a real pharmacologist should:

Getting back to other differences even within a given species is that the initial, non-conjugative metabolism of MDMA is mediated by CYP2D6, a notoriously polymorphic enzyme. In humans, there are significant interethnic differences in 2D6 activity: ~75 allelic variations that are grouped into four phenotypes: poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). (nice free full-text review, albeit in the oncology setting, by CYP clinical pharm guru David Flockhart and colleagues.)
So, if there is toxicity in humans, it is important to consider whether the parent MDMA or any number of its metabolites are neurotoxic and whether there are correlations of toxicity with individuals any of the four phenotypes. As if that is not complicated enough, the methylenedioxy group (the MD of MDMA) is notorious for mechanism-based inhibition of P450 activities and I’m having trouble thinking of whether this would be have more or less influence on a poor or ultra-rapid metabolizing individual.

Hammer meet head of nail.