Tolmetin Sodium

Tolmetin sodium, a non-steroidal anti-inflammatory drug, inhibits hepatic tryptophan 2,3-dioxygenase (TDO) activity in rats following intraperitoneal administration at 5 mg/kg/day for 5 days. TDO is a rate-limiting enzyme in tryptophan catabolism that regulates the physiological flux of tryptophan into metabolic pathways including serotonin and melatonin synthesis. By inhibiting TDO activity, tolmetin increases the availability of tryptophan for serotonin production. The study demonstrated that tolmetin treatment significantly increased serotonin levels in the hippocampus. In contrast, tolmetin significantly reduced dopamine levels in the striatum. Tolmetin also increased the amount of melatonin produced by the pineal gland. These results indicate that tolmetin’s pharmacological effects extend beyond cyclooxygenase inhibition to include modulation of the tryptophan-kynurenine pathway and neurotransmitter systems.

Fig. 1 Effect of tolmetin on liver TDO activity. (Dairam A.; et al. 2006)

Tolmetin sodium rectal mucoadhesive hydrogels were developed using various polymers including hydroxypropylmethyl cellulose, hydroxylethyl cellulose, carboxymethyl cellulose and sodium alginate at different concentrations. The optimized CMC 2% w/w hydrogel exhibited suitable pH (6.64-7.75), gel strength of 65.29 seconds, and sustained drug release reaching 72 to 92.6 percent after 8 hours following diffusion-controlled mechanism. All formulations showed zero-order degradation kinetics except sodium alginate hydrogel. The CMC hydrogel demonstrated relative bioavailability of 357.93 percent compared to commercially available capsules, with good in vitro-in vivo correlation confirmed by histopathological studies.

Fig. 2 Tolmetin Sodium mean plasma concentration-time curve after oral administration of Rumatol capsule and rectal administration of F8 hydrogel to six rats. (Ramadan A A.; et al. 2018)