Metabolism of 6-chloro-5-cyclohexyl-1-indancarboxylic acid (TAI-284), a new non-steroidal anti-inflammatory agent, after repeated administration in rats and mice

1 Whole-body autoradiography showed that a single oral administration of TAI-284-14C to rats caused a rapid and wide distribution of radioactivity in tissues, with the peak levels at 2 hr in most tissues. At this time, relatively higher concentrations were noted in the kidney, liver, lung, blood and heart, while no detectable amount of radioactivity was present in the brain, spinal cord and eye-ball. Radioactivity declined to low levels at 24 hr in most tissues, but the levels in the kidney, liver, lung and blood were still relatively high. 2 During daily oral administration of TAI-284-14C, only a slight increase in plasma radioactivity 2 and 24 hr after dosing was observed. The larger part of the radioactivity still in the body 24 hr after administration was recovered from the intestinal contents, a small amount being in the tissues. Dosing of TAI-284-14C for 7 days caused no appreciable increase in tissue radioactivity, except in the intestine, where the radioactivity increased to 2.3 times that noted after a single administration. After daily oral administration of TAI-284-14C, the cumulative excretion closely paralleled the dosage of radioactivity. Excretion was completed within 3 days after discontinuing medication. 3 Pretreatment of mice with phenobarbital activated the metabolism of aminopyrine, p-nitroanisole, TAI-284-14C, pentobarbital and zoxazolamine. TAI-284 increased only the metabolism of aminopyrine, while diclofenac did not induce the metabolism of these five compounds. (auth.)