BLOCK DRUG OTC BC POWDER: CONTRIBUTION OF SALICYLAMIDE

BLOCK DRUG OTC BC POWDER: CONTRIBUTION OF SALICYLAMIDE to the aspirin/caffeine/salicylamide analgesic product is demonstrated in a recently conducted pharmacokinetic study, the firm maintained in a Jan. 6 letter to FDA. "We believe that this study demonstrates that the inclusion of salicylamide in . . . BC Analgesic Powder increases the plasma concentration of aspirin resulting in a more rapid bioavailability of this analgesic ingredient," Block said. Under the analgesic tentative final monograph, salicylamide and all other analgesic adjuvants are classified in Category III. Block is requesting a meeting with FDA to discuss what, if any, additional studies would be necessary to upgrade the ingredient to Category I in the final monograph. The TFM came out in November 1988, with a cut off date of November 1989 for new data submissions. The pharmacokinetic study compares levels of aspirin, salicylamide, and their metabolites in 13 subjects taking BC Powder (acetylsalicylic acid 650 mg, salicylamide 195 mg, caffeine 32 mg), BC minus acetylsalicylic acid, and BC minus salicylamide. The study design included a fourteen day washout period between each treatment regimen in the crossover study. The study found that maximum plasma concentration of acetylsalicylic acid occurred as early as 10 minutes after ingestion of BC powder and the area under the curve was "more than five-fold that of the aspirin plus caffeine formulation without salicylamide." The study also found that the maximum concentration of salicylamide after taking BC occurred in 10 minutes with a 76 minute half-life, while the maximum concentration in the salicylamide plus caffeine group occurred at 30 minutes with a half-life of 42 minutes. Results of the study, the firm concluded, "demonstrate that salicylamide in the BC formula decreases the rate of hydrolysis of acetylsalicylic acid to salicylic acid and enhances the plasma levels of acetylsalicylic acid with an associated increase in the elimination half-lives of the parent compounds." Block noted that salicylamide may increase the area under the curve by competing with acetysalicylic acid for binding to plasma proteins. "The competitive protein binding by salicylamide may be enough to contribute to enhancing the analgesic efficacy of the combination drug," the firm said. Block also submitted a protocol plan for use, if necessary, to establish the contribution of salicylamide in reducing pain. The proposed study would compare BC powder to aspirin plus caffeine, salicylamide, and placebo in 160 patients after third molar extraction.