Effects On Animals
The effects of Benoxaprofen on animals were tested in a series of experiments. Benoxaprofen had a considerably anti-inflammatory, analgesic and also anti-pyretic activity in those tests. In all six animals tested, which included rats, dogs, rhesus monkeys, rabbits, guinea pigs and mice, the drug was well absorbed orally. In three of the six species benoxaprofen was then effectively taken up from the gastrointestinal tract (after oral doses of 1–10 mg/kg). The plasma half life was found to be different, being less than 13 hours in the dog, rabbit and monkey, it was notable longer in mice. Furthermore there were species differences found in the rate and route of excretion of the compound. Whereas benoxaprofen was excreted into the urine by the rabbit and guinea pig, biliary excretion was the way of clearance found in rats and dogs. In all species only unchanged benoxaprofen was found in the plasma mostly extensively bound to proteins.
The excretion of the unchanged compound into the bile did occur more slowly in rats. This is interpreted by the authors as evidence that no enterohepatic circulation takes place. Another research in rats showed that the plasma membrane of hepatocytes begun to form blebs after administration of benoxaprofen. This is suggested to be due to disturbances in the calcium concentration which is possibly a result of an altered cellular redox state which can have an effect on mitochondrial function and therefore cause disturbances in the calcium concentration. In none of the species significant levels of metabolism of benoxaprofen were found to have happened. Only in dogs glucuronide could be found in the bile which is a sure sign of metabolism in that species. Also no differences in distribution of the compound in normal and pregnant rats were found. It was shown in rats that benoxaprofen was distributed into the foetus but with a notable lower concentration than in the maternal tissue.
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