RESUMEN

The efficacy of a novel transdermal patch containing tropisetron, a 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonist, against emesis induced by anticancer agents were evaluated, in comparison with the effect of traditional tropisetron injection, in rats. The antiemetic effects were assessed via the inhibitory activity on the anticancer agent-induced kaolin-consuming behavior, a pica model representing vomiting in emesis-resistant rodents. The tropisetron patch (10mg/patch, 3.5cm(2)) was attached on the shaved back area of rats. Eight h later, each anticancer agent, cisplatin (10mg/kg, i.v.), cyclophosphamide (200mg/kg, i.p.) or doxorubicin (8mg/kg, i.v.), was administered, and thereafter, daily kaolin consumption was measured for 3 days. In comparison, the effect of daily injection of tropisetron (2mg/kg, i.v.), given 10min, 24 and 48h after the anticancer agent administration, was also evaluated. Kaolin intake greatly increased to 21, 17 and 10 folds of control ingestion on the first day after administration with the anticancer agents, cisplatin, cyclophosphamide and doxorubicin, respectively, and then gradually decreased to near control level on day 3. Such anticancer agent-induced increases in the kaolin consumption were remarkably attenuated by the attachment of tropisetron patch, resulting in the reduction to half levels, which is comparable to the efficacy of daily tropisetron injection. In particular, the blood concentration of tropisetron following patch attachment reached a maximum level of 30-40ng/ml in 12h and exhibited a plateau until detachment of the patch, in contrast to a rapid elimination with a half-life of 2.21h after injection of the drug. Taken together, it is suggested that the novel tropisetron patch could be a promising regimen for the relief of emesis, based on the long-term antiemetic effects on the diverse anticancer agents and the convenience to use the transdermal delivery system for the cancer patients who have difficulty in taking drugs due to surgical operation or gastrointestinal dysfunction.