Nano-formulated indomethacin at lower dose effective in treating pain

A novel, lower-dose formulation of indomethacin, a widely used pain reliever, is absorbed faster by the body than a standard formulation and maintains comparable maximum concentrations in the blood despite being administered at a lower dose, according to a study to be reported here tomorrow at the annual meeting of the American Headache Society (AHS).

The presentation of the study marked the first disclosure at a clinical congress of data from a broader research program that is reformulating a large class of marketed analgesics by means of nanotechnology. Nano-formulations reduce drug-particle size to enhance drug dissolution in the body.

In this Phase I pharmacokinetic study, nano-formulated indomethacin in doses of 20 mg or 40 mg demonstrated a faster time to maximum concentration (T_max) than a 50-mg dose of standard indomethacin. Among patients who fasted ahead of drug administration, the maximum concentration (C_max) was comparable for 40-mg nano-formulated indomethacin and 50-mg standard indomethacin, and lower for all other doses and feeding states in the study.

As anticipated, under both fasting and fed states, total drug exposure (AUC) was reduced by about 25% when the study subjects received 40-mg nano-formulated indomethacin instead of 50-mg standard indomethacin. Half-life (T_1/2) was comparable across all doses, formulations, and feeding states, though slightly higher for 50-mg standard indomethacin under fasting conditions.

Indomethacin, which has been used in various indications for decades, is a member of one of the largest classes of pain medicines, called non-steroidal anti-inflammatory drugs (NSAIDs). To lower the potential for adverse events associated with NSAIDs, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have advised that NSAIDs should be used at their lowest effective dose for the shortest duration of time.

"These early data indicate the promise of re-formulating NSAIDs through nanotechnology," said Stephen Silberstein, M.D., Professor of Neurology and Director of the Jefferson Headache Center at Thomas Jefferson University. "It is important now to progress studies evaluating the clinical benefit of these compounds."

Dr. Silberstein continued, "NSAIDs are a mainstay in the treatment of pain, and new formulations to speed pain relief would be a welcome advance in analgesia. Lowering doses may also improve the tolerability and safety of this commonly used class of drugs."