Abstract
Oral doses of 2.5 mg/kg of naproxen in beagle dogs were found to be rapidly and completely absorbed. In the dog, the sodium and calcium salts of naproxen were absorbed significantly faster than the non-micronized form of naproxen, while the micronized drug could not be distinguished from either the salts or the macro from. Area responses to intravenous and oral doses of naproxen in two human subjects showed that oral doses of 200 and 250 mg were apparently one hundred percent absorbed. In a comparison of the amount and rate of absorption of naproxen form capsules and tablet formulation variants, no significant difference in either of the parameters could be detected. These results indicated that capsules and tablets were identical in absorption characteristics and furthermore that neither increasing the concentration of magnesium stearate nor changing the tablet lubricant to stearic acid had any effect on availability. Similarly, the tablet formulation with an extraordinarily long disintegration time and the tablet formulated with an alkalinizing agent were not significantly different from the other tablets or the capsules. A comparison of the results obtained from oral administration of 200 mg of naproxen taken by volunteer subjects in three forms, suspensions, capsules and tablets, revealed an apparent rise in the absorption rate constant with the suspension from but no difference in the amount of drug absorbed. It was suggested that more rapid dissolution of the drug in the wetted and well dispersed form explained the faster appearance of naproxen in the plasma. In a second tablet formulation study where the relative amounts of naproxen and lactose were altered, the drug was absorbed to the same extent, and at the same rate regardless of the fraction of total tablet weight that was naproxen. Finally, although differences in absorption rate constants were not statistically significant, naproxen appeared to be more rapidly absorbed in fasted subjects than in those who took the drug with food. However, there was no diminution in the amount absorbed in the non-fasted subjects.
