CORVALLIS, Ore. - Providing safe, effective pain control for ailing elephants has frustrated zoos and sanctuaries for decades, but researchers at Oregon State University have zeroed in on relief for the colossal creatures.

While it's long been known that ibuprofen and phenylbutazone are effective pain killers, no one really knew just how much to give an elephant. But Ursula Bechert, an OSU doctor of veterinary medicine in the College of Science, and John Mark Christensen, an associate professor in OSU's College of Pharmacy, have calculated the optimal therapeutic dose levels of both ibuprofen and phenylbutazone for elephants, both common pain medications used in large animals.

In the past, caregivers had just commonly "scaled-up" doses of medications, taking guidelines used in other animals and increasing them based on size differences, Bechert said.

And while the technique did provide relief, the doses were far from optimal, with animals often receiving far less medicine than needed to effectively treat pain and inflammation, Christensen said.

"The problem with scaling up the doses from those found effective in, say horses and other animals, is that it doesn't take into account the metabolic differences between the animals," Bechert said.

The OSU team found the effective dose of ibuprofen is six milligrams per kilogram of weight for Asian elephants and seven milligrams per kilogram for African elephants, given every 12 hours. It isn't much different than the standard human dose, except humans metabolize the drug much faster, Christensen said. In humans, the therapy is repeated every four to six hours.

"With medications such as ibuprofen, the drugs have a longer half-life in elephants. The medicine stays in their body longer. That's what you expect in larger animals," he said.

For phenylbutazone, the optimal dose is three milligrams per kilogram for both Asian and African elephants, but Asian elephants need dosing every 48 hours, compared to every 24 hours in African elephants.

When too little of either medication is given, pain relief is short-lived or non-existent. Overdoses waste money and can endanger animal health.

Problem pain areas in captive elephants are often the feet and joints, Bechert said.

While researchers aren't certain why some captive populations suffer more than their wild cousins, some researchers have theorized that a relatively sedentary lifestyle could be part of the problem, she said.

In the wild, elephants can roam up to 40 or more miles a day, trekking across dirt, sand and other surfaces. But captive elephants, with no need to search out food and water, are typically restricted to much smaller areas.

One of the problems in finding effective doses of pain relief is that it is often difficult to determine how pain and inflammation affects each individual animal, Bechert said. She and Christensen tallied keeper's observations to assess the level of pain controlled by various dosing schedules.

But the scientists also ran pure quantitative studies to analyze blood serum samples taken at various time intervals after administration.

Some of the results surprised the researchers.

"Asian and African elephants are really quite different animals, both in their metabolism and their appearance. I was really quite surprised at the differences between the animals," Christensen said. "And in appearance, the Asian has a rounder head, smaller ears, larger and rounder abdomens and smaller legs."

Both ibuprofen and phenylbutazone - commonly known as bute - affect prostaglandins in the body. Prostaglandins are the chemicals responsible for pain, swelling and inflammation and are produced in response to injury or illness.

While bute and ibuprofen can be very effective in pain relief, like most drugs, both can be dangerous if improperly administered. Kidneys and the gastrointestinal systems in particular can be damaged by the wrong dose of either medicine.

More than 130 Asian elephants and 150 African elephants live in about 80 zoos in North America. Most were imported in the 1960s and early 1970s.

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Ursula Bechert,