Effects of probenecid, methotrexate, digoxin and verapamil on the renal excretion of dicycloplatin in rats

Aim: To compare the effects of the drug transporter substrates such as probenecid, methotrexate, digoxin and verapamil on renal excretion of dicycloplatin in rats. Method: The concentration of dicycloplatin in urine was measured by atom absorption and cumulate excretion amount of dicycloplatin in the initial 4 h period was evaluated. Results: The excretion amount of dicycloplatin in urine decreased after substrates of the drug transporters were coadministrated. In the initial 4 h period, the total urinal excretion percentage of dicycloplatin after iv injection of dicycloplatin were (70.7 ± 9.8) %, but co-injection of dicycloplatin with probeneside, verapamil, digoxin and methotrexate was responsible for the urinal excretion of platin of (28.8 ± 4.1) %, (34.2 ± 10.1) %, (43.6 ± 2.8) % and (47.4 ± 8.5) %, respectively. Moreover, renal platin concentration changed from (278.8 ± 112.0) to (179.6 ± 122.2), (309.5 ± 88.8), (374.4 ± 90.1), (266.0 ± 107.5) μg/g, respectively. Conclusion: Drug transporter substrates as probeneside and verapamil reduce the renal excretion of platin when they were used in combination with dicycloplatin. P-gp, OAT or OATP may take part in the excretion of platin.