Abstract
To examine the drug interaction between LC9018 and tegafur, the tegafur was administered to LC9018 treated or control mice and plasma concentrations of tegafur and its active metabolite, 5-fluorouracil (5-FU) were monitored.
1. In 300μg LC9018/animal (intravenous, i.v.) treated group, the maximum plasma level(Cmax) of 5-FU and the area under the curve (AUC)decreased to 43% and 64% of control values, respectively. On the other hand, no change was observed in tegafur level, suggesting that LC9018 inhibited the conversion of tegafur to 5-FU at this dose.
2. In 300μg LC9018/animal (intrapleural, i. pl.) treated group, 5-FU level decreased to 55% of the control at 30min after administration. But the influence on the metabolism of tegafur was smaller compared to the intravenous treatment of LC9018.
3. In 180μg/animal (i.v.), 150μg/animal (i.pl.) and 300μg LC9018/animal (subcutanous, s.c.) treated groups, both tegafur and 5-FU level did not alter compared to the control.
4. From above results, influence of LC9018 on the metabolism of tegafur depends on the dose and the administration route (i.v.> i.pl.> s.c.). It is considered that LC9018 slightly affects the metabolism of tegafur at clinical dose (200μg/animal i.pl.).
