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

Marshall P. Goren, Lowell B. Anthony, Kenneth R. Hande, David H. Johnson, Wolfgang P. Brade, Mark W. Frazier, Dorothy A. Bush, Jackie T. Li

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)616-621
Number of pages6
JournalJournal of Clinical Oncology
Volume16
Issue number2
StatePublished - Feb 1998

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Mesna
Ifosfamide
Lung Neoplasms
Pharmacokinetics
Tablets
Oral Administration

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Goren, M. P., Anthony, L. B., Hande, K. R., Johnson, D. H., Brade, W. P., Frazier, M. W., ... Li, J. T. (1998). Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide. Journal of Clinical Oncology, 16(2), 616-621.

Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide. / Goren, Marshall P.; Anthony, Lowell B.; Hande, Kenneth R.; Johnson, David H.; Brade, Wolfgang P.; Frazier, Mark W.; Bush, Dorothy A.; Li, Jackie T.

In: Journal of Clinical Oncology, Vol. 16, No. 2, 02.1998, p. 616-621.

Research output: Contribution to journalArticle

Goren, MP, Anthony, LB, Hande, KR, Johnson, DH, Brade, WP, Frazier, MW, Bush, DA & Li, JT 1998, 'Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide', Journal of Clinical Oncology, vol. 16, no. 2, pp. 616-621.
Goren, Marshall P. ; Anthony, Lowell B. ; Hande, Kenneth R. ; Johnson, David H. ; Brade, Wolfgang P. ; Frazier, Mark W. ; Bush, Dorothy A. ; Li, Jackie T. / Pharmacokinetics of an intravenous-oral versus intravenous-mesna regimen in lung cancer patients receiving ifosfamide. In: Journal of Clinical Oncology. 1998 ; Vol. 16, No. 2. pp. 616-621.
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abstract = "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.",
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AU - Anthony, Lowell B.

AU - Hande, Kenneth R.

AU - Johnson, David H.

AU - Brade, Wolfgang P.

AU - Frazier, Mark W.

AU - Bush, Dorothy A.

AU - Li, Jackie T.

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N2 - 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.

AB - 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.

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