Journal of Clinical Oncology, Vol 16, 616-621, Copyright © 1998 by American Society of Clinical Oncology
Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide
MP Goren, LB Anthony, KR Hande, DH Johnson, WP Brade, MW Frazier, DA Bush and JT Li
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
PURPOSE: To compare the pharmacokinetics of the approved I.V. (intravenous)
mesna regimen and an investigational I.V.-oral regimen that could be used
in outpatients who receive ifosfamide. PATIENTS AND METHODS: The I.V.
regimen consisted of three I.V. mesna doses given at 0, 4, and 8 hours
after ifosfamide administration. The investigational regimen included an
I.V. mesna dose given concurrently with ifosfamide, followed 2 and 8 hours
later by oral administration of mesna tablets. I.V. 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
I.V.-oral or I.V. mesna regimen on 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 I.V.-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
I.V.-oral than the I.V. regimen. CONCLUSION: These pharmacokinetic data
show that the I.V.-oral regimen should be at least as uroprotective as the
I.V. mesna regimen. Patients may also benefit from the I.V.-oral regimen
because of the higher trough values during hours 0 through 12 and the
sustained urinary mesna excretion during hours 12 through 24.
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