Evaluation of intramuscular lateral distribution profile of topically administered acetaminophen in rats.

To clarify to what extent topically administered drug molecules horizontally permeate into tissues surrounding the administration site, the intramuscular lateral concentration profile of acetaminophen was investigated in vivo using the microdialysis method in rats. When acetaminophen was intramuscularly administered for 6 h in a pinpoint manner at a constant rate of 3 microg/min, it was clearly detected in the muscle surrounding the administration site, being 17.5 microg/ml when measured at a 2 mm distance from the administration site. The concentration in the muscle was decreased as the distance increased, and those measured at 5 mm and 40 mm were 0.35 microg/ml and 0.09 microg/ml, respectively. In addition, it was shown that the concentration in the muscle at 40 mm reflected the compound's concentration in plasma, but not the compound's horizontal permeation from the administration site. With these observations, the intramuscular distribution profile of acetaminophen was numerically characterized according to Fick's law. As a result, it was revealed that horizontal permeation is the primary process accountable for the increased intramuscular concentration only in the area adjacent to the administration site, and the radius of the adjacent area was calculated to be 5.80 mm for acetaminophen.