AS ABUSE OF PAINKILLERS CLIMBS, OXYCONTIN GETS REFORMULATED

To Thwart Improper Use, Pain Therapeutics' Version Can't Be Dissolved,
Crushed

A California biotechnology company has taken a small step toward
developing an "abuse-resistant" form of the painkiller OxyContin,
joining a broader effort to prevent recreational use of prescription
pain medications.

Abuse of prescription pain drugs has risen sharply over the last
several years, thanks in part to wider availability of the drugs and a
profusion of shady Internet-based pharmacies that don't ask for
prescription slips. According to a federal survey of drug use, 2.4
million Americans began nonmedical use of prescription painkillers in
2001, more than quadruple the number in 1990.

The problem is especially acute where long-lasting painkillers such as
OxyContin are concerned. OxyContin -- which last year produced sales
of almost $2 billion for its maker, closely held Purdue Pharma LP,
Stamford, Conn. -- can be easily crushed and then dissolved in liquid
or snorted. That process delivers a 12-hour dose of the drug in a
matter of minutes, creating an intense high.

Oxycontin recently lost patent protection, potentially paving the way
for greater abuse with cheaper generics, but also presenting an
opportunity for reformulated versions of the drug.

Drug makers have tried for years to develop ways of preventing abuse
of prescription drugs, but the road has been challenging. One of the
chief obstacles is that, by engineering abuse resistance into the
painkillers themselves, the medications are often rendered less
effective. One approach, for instance, is to pair oxycodone, the
active ingredient in OxyContin, with a substance that blocks its
effect if the drug is injected or inhaled. But the resulting
medication doesn't always work as well, and can sometimes tip habitual
painkiller users into narcotic withdrawal.

Pain Therapeutics Inc., a small biotech company in South San
Francisco, Calif., has taken a different path. The company's
experimental drug Remoxy is a reformulated version of oxycodone
designed to frustrate casual attempts to liberate the active
ingredients. The company mixes oxycodone with three other substances
it declines to identify, yielding a viscous fluid that Pain
Therapeutics says won't release the oxycodone when crushed or
dissolved in water or alcohol. Taken normally, the company says, the
drug is still slowly released in a 12-hour period through the stomach
and intestinal lining.

Earlier this year, the company began a small clinical trial in Britain
that attempted to simulate the process of OxyContin abuse. In one
test, 10 volunteers swallowed two ounces of vodka containing either
crushed OxyContin or ground-up Remoxy. Researchers carefully monitored
the volunteers and charted their blood levels of oxycodone, eventually
concluding that the Remoxy group had less than half as much oxycodone
in their system as the OxyContin group.

Similar effects were seen when the volunteers were asked to chew the
medications, which also usually releases oxycodone quickly. Such tests
of new painkillers are not uncommon.

J. David Haddox, a Purdue vice president for health policy, declined
to comment specifically on the Pain Therapeutics test. Dr. Haddox,
however, questioned whether the design of such trials should be
discussed openly, since the information might lead to further drug
abuse. "I'm loath to tell people how to abuse medications in the
newspaper," he said.

"We do not think abuse resistance and therapeutic use are mutually
exclusive," said Pain Therapeutics Chief Executive Remi Barbier. "For
the first time ever, there is really a safer version of oxycodone."

While heartening to the company, the trial results won't be enough to
convince everyone that Remoxy is truly abuse resistant. Some
researchers argue that a 10-person trial is too small to yield solid
proof of the drug's properties. Mr. Barbier said the results from the
United Kingdom test were statistically significant, meaning they met
established criteria that distinguish meaningful data from random noise.

Mr. Barbier acknowledged that some people may still find a way to
abuse Remoxy, although he said it would require some knowledge of
chemistry. "This is not abuse-proof," he said. "All we're trying to do
is to raise the hurdle so high that abusers will stop taking oxycodone."

Outside researchers hadn't seen the Pain Therapeutics data and
generally declined to comment on the results. The company plans to
announce them today, and intends to present them formally at a
scientific meeting in September. By the end of this year, Mr. Barbier
said, the company plans to begin a large late-stage trial designed to
prove that Remoxy works as well as OxyContin.