Pharmacokinetic Study of Topical Ketoprofen in Women
Minori Kinjo
School of Pharmacy, University of Maryland, Baltimore

Rheumatoid arthritis (RA) is the most common type of arthritis that affects about 2.5 times more women than men. Approximately 1.5 million women in the United States suffer from daily joint pain, which is an inevitable consequence of this disease. Effective management of pain in women with RA, considering the frequency and impact on mental health, is very important. The non-steroidal anti-inflammatory drugs (NSAIDs) represent a group of analgesic, anti-inflammatory, anti-pyretic agents that are very effective in treating acute and chronic pain. NSAIDs such as naproxen, ibuprofen, and aspirin are available as over-the-counter drugs, however, their use can be limited by potential adverse effects caused by irritation and ulceration of the gastro-intestinal mucosa. In order to bypass these side effects, topical gel formulations have been developed, and among these readily available NSAIDs, ketoprofen possesses physiochemical characteristics that are more suitable for transdermal administration.

Previously, we have conducted a pharmacokinetic study to compare the relative bioavailability 20% ketoprofen PLO after single and multiple dosing, applied to intact skin on the upper arm, compared to an oral dose of 50 mg. ketoprofen in healthy male subjects. Multiple-dose topical administration of ketoprofen PLO results in significant systemic absorption achieving therapeutic concentration. Due to the low relative bioavailability of topical ketoprofen, it is unlikely that sufficient drug will be absorbed following multiple dosing to put the patient at risk for toxicities. Therefore, 20% ketoprofen PLO is an effective alternative drug of choice for RA patients.

Most pharmacokinetic studies, especially phase I trials, are carried out in healthy male volunteers despite changes in 'The 1993 FDA Gender Guidelines.' Since detailed pharmacokinetic studies are not a part of phase III trials, effects of gender differences in pharmacokinetics are often not known. Differences in physiological compositions of the skin and epidermal structures between males and females likely exist, and pharmacokinetic characteristics of drug via transdermal delivery may differ not only because of the physiochemical characteristics of drug, but also because of gender differences.

The proposed research is innovative, especially because gender difference was never explored for its systemic absorption of topical NSAIDs such as ketoprofen. The successful completion of this research will allow us to identify the optimal dosing strategy to be used in RA patients, and also will be the foundation for the next step of assessment to evaluate clinical efficacy of topical ketoprofen in RA patients. It is our expectation that this project will provide significant new information regarding the likelihood of using topical ketoprofen for systemic pain management in women with RA, and may also provide patients with a safe alternative to oral drug delivery systems.