"Our objective was to take what we already knew about the pharmacokinetics of acetaminophen and go a step further," explained lead investigator Cathy K. Gelotte, PhD, Executive Director, Medical and Regulatory Product Development, McNeil Consumer & Specialty Pharmaceuticals. "We wanted to see if acetaminophen is cleared at the same rate when we increased dosage beyond the recommended maximum adult daily dose of 4 g/day to 8 g/day. This study demonstrates how the body handles a higher dose and may be useful data for physicians."

The study, a double-blinded, placebo-controlled design, examined the pharmacokinetics of three dosing regimens: 4 g/day, 6 g/day, and 8 g/day. A total of 36 subjects were divided into two groups. Group I included 6 patients on placebo and 12 on acetaminophen taking 4 g/day then 6 g/day. Group II included 6 patients on placebo and 12 patients on acetaminophen taking 4 g/day then taking 8 g/day. Regimens were continued for three consecutive days, with blood sampling during the first and last dose of each daily regimen.

"Analysis of plasma acetaminophen levels showed that doses as high as 8 g/day, or twice the maximum daily recommended dose, did not accumulate and the drug was consistently cleared from the bloodstream," said Dr. Gelotte. "Moreover, it is important to note that liver enzyme values for all subjects, regardless of whether they were on the 4-, 6-, or 8 g/day regimen, stayed within normal limits throughout the study."

Dr. Gelotte emphasized that this study was undertaken to learn more about the pharmacokinetic profile of acetaminophen. It was not intended to explore the potential for increa
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Contact: Robert Murphy
rmurphy@djstorch.com
908-273-1400
D. J. Storch & Associates Inc.
1-Apr-2003