Abstract
Some non-steroidal anti-inflammatory drugs (NSAIDs) exhibit sex differences in their pharmacokinetics or pharmacodynamics; pharmacokinetic studies of tolmetin, a potent NSAID used for relief of moderate pain in rheumatoid arthritis, have hitherto been carried out only in males. Here, the pharmacokinetics of tolmetin was studied after an oral administration of 10 mg kg−1 of tolmetin sodium in both male and female Wistar rats. Blood samples were obtained at selected times during 4 h after medication, and tolmetin concentrations were determined by high-performance liquid chromatography. After administration of tolmetin, blood concentrations increased rapidly, reaching the maximal concentration in about 0.3 h in both male and female rats. Then, blood concentrations decayed with a significantly different terminal half-life between male and female rats. In males a half-life of about 0.9 h was observed, whereas in females it was about 3.3 h. The area under the tolmetin blood concentration-time curve for female rats was also significantly higher man that of male rats. These results strongly suggest a sex-related difference in the pharmacokinetics of tolmetin and could reflect differences in isoenzymes of cytochrome P450 that metabolize tolmetin.
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