Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide

Purpose: To compare the pharmacokinetics of the approved IV (intravenous) mesna regimen and an investigational IV-oral regimen that could be used in outpatients who receive ifosfamide. Patients and Methods: The IV regimen consisted of three IV mesna doses given at 0, 4, and 8 hours after ifosfamide administration. The investigational regimen included an IV mesna dose given concurrently with ifosfamide, followed 2 and 8 hours later by oral administration of mesna tablets. IV and oral mesna doses equaled 20% and 40%, respectively, of the ifosfamide dose. The study subjects were 12 lung cancer patients who received ifosfamide 1.2 g/m² daily for 5 days. The patients were randomized to receive either the IV-oral or IV mesna regimen off day 1, followed by crossover to the other regimen on days 2 through 5 of ifosfamide treatment. The urinary profiles of mesna and dimesna excretion were determined on days 1,2, and 5; pharmacokinetic parameters for blood samples were determined only on day 5. Results: During the first 12 hours after ifosfamide administration, the amount of mesna excreted and the profile of urinary mesna excretion was similar for both regimens; however, the IV-oral regimen showed less fluctuation in the excretion rate and higher trough values. During hours 12 to 24, about eightfold more mesna was excreted by patients given the IV-oral than the IV regimen. Conclusion: These pharmacokinetic data show that the IV-oral regimen should be at least as uroprotective as the IV mesna regimen. Patients may also benefit from the IV- oral regimen because of the higher trough values during hours 0 through 12 and the sustained urinary mesna excretion during hours 12 through 24.