Table 1.

Effects of NSAIDs or celecoxib in animal models

ModelSpeciesNSAID (ppm)Relative Efficacy (%↓)HEDRef.
AOM colonratsNaproxen (400 ppm)++ (60%)320 mg13
AOM colonratsAspirin (200 ppm)+ (20%)160 mg21
AOM colonratsAspirin (1,800 ppm)++ (60%)1,440 mg21
AOM colonratsCelecoxib (1,500 ppm)++++ (96%)1,200 mg16
AOM colonratsCelecoxib (1,500 ppm)+++ (84%)1,200 mg17
AOM colonratsCelecoxib (500 ppm)++ (67%)400 mg17
Min intestinemiceAspirin (250 ppm)++ (55%)265 mg31
Min intestinemiceCelecoxib (1,500 ppm)+++ (70%)1,590 mg28
UV skinmiceCelecoxib (500 ppm)+++ (70%)533 mg39
UV skinmiceCelecoxib (150 ppm)++ (60%)160 mg39
UV skinmiceIndomethacin (4 ppm)+++ (70%)4.3 mg39
UV skinmiceNaproxen (400 ppm)+++ (70)427 mgUnpublished data
OHBBN bladderratsCelecoxib (1,000 ppm)++++ (90%)800 mg36
OHBBN bladdermiceCelecoxib (1,250 ppm)++++ (90%)1,333 mg36
OHBBN bladderratsNaproxen (400 ppm)++++ (87%)320 mg35
OHBBN bladderratsAspirin (300 ppm)0240 mg35
OHBBN bladderratsAspirin (3,000 ppm)++ (65%)2,400 mg35

NOTE: The calculations below are standard scaling factors that would be used for the FDA. They do not take into account specific pharmacokinetics of individual agents which can only properly be done after gavage dosing.

HEDs were calculated as follows, using 100 ppm (100 μg/g diet) as an example. Rats, which eat 15 g food daily, would consume 1.5 mg drug; for a 250 g rat, the daily weight-based dose would be 6 mg drug/kg body weight. Dividing by the rat-to-human scaling factor of 6, the HED is 1 mg/kg body weight; for an 80 kg human this is 80 mg. Mice, which eat 4 g food daily, would consume 0.4 mg drug; for a 25 g mouse, the daily weight-based dose would be 16 mg drug/kg body weight. Dividing by the mouse-to-human scaling factor of 12, the HED is 1.33 mg/kg body weight; for an 80 kg human this is 106 mg.

Abbreviation: HED, human equivalent dose.