Abstract
Pharmacological interactions among noosteroidal antiinflammatory drugs were studied by determining their hypothermic action and acute toxicity in mice, and their antipyretic action in adjuvant-induced fever rats. 1) The hypothermic actions of the combined use of naproxen with aminopyrine (a), indomethacin with aminopyrine (b), and phenylbutazone with aminopyrine (c) in mice were additive. 2) The antipyretic action of (a) in adjuvant-induced fever rats was additive. 3) The acute toxicities of (a), (b), and (c) were found to be partially antagonistic or antagonistic by estimation according to the diagram proposed by Guddum. 4) The safety indices of the analgesic actions of (a), (b), and (c) were calculated on the basis of 50% analgesic effective dose and 50% lethal dose. The index values of (a), (b), and (c) were 49.6, 11.1, and 5.8, respectively. These and previous results suggested that the combined use of aminopyrine, a weak basic drug, with some weak acidic nonsteroidal anti-inflammatory drugs (e.g. naproxen) was benefrcial.
