Abstract
1. We investigated the pharmacokinetics of ifosfamide 5 g m-2 given by two regimens. Six patients (one female), median age 55 (range 40-71) years, all with lung cancer received 5 g m-2 ifosfamide (median ifosfamide dose 8.95 g) as an intravenous infusion over 0.5 h with mesna. Four other cancer patients (all male) of median age 52.5 (range 23-72) years were studied on seven treatment occasions with 5 g m-2 ifosfamide (median ifosfamide dose 8.88 g) as a 24 h intravenous infusion with mesna. Plasma was assayed for ifosfamide by gas liquid chromatography and for alkylating activity by the nitrobenzylpyridine method. 2. After ifosfamide 5 g m-2 infused over 0.5 h, the decay of the plasma ifosfamide concentration was monoexponential with a median (range) t1/2,z of 5.4 h (3.6-10.4 h). The median clearance was 60 ml min-1 (47-104) and the median volume of distribution was 388 (329-783) ml kg-1. Plasma nitrobenzylpyridine alkylating activity showed a biexponential decay in four patients and a monoexponential decay in two, with a median AUC of 102 (24-177) nmol nor nitrogen mustard eq h ml-1. 3. When ifosfamide 5 g m-2 was given as a 24 h infusion, the decay of the plasma ifosfamide concentration was monoexponential, the median (range) t1/2,z was 4.5 (3.4-6.1), the median volume of distribution was 563 (292-818) ml kg-1 and the median clearance was 79 (59-116) ml min-1. Plasma nitrobenzylpyridine alkylating activity decayed monoexponentially and the median AUC was 49 (45-131) nmol nor nitrogen mustard eq ml-1 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allen L. M., Creaven P. J., Nelson R. L. Studies on the human pharmacokinetics of isophosphamide (NSC-109724). Cancer Treat Rep. 1976 Apr;60(4):451–458. [PubMed] [Google Scholar]
- Brade W. P., Herdrich K., Varini M. Ifosfamide--pharmacology, safety and therapeutic potential. Cancer Treat Rev. 1985 Mar;12(1):1–47. doi: 10.1016/0305-7372(85)90011-8. [DOI] [PubMed] [Google Scholar]
- Brock N., Hoefer-Janker H., Hohorst H. J., Scheef W., Schneider B., Wolf H. C. Die Aktivierung von Ifosfamid an Mensch und Tier. Arzneimittelforschung. 1973 Jan;23(1):1–14. [PubMed] [Google Scholar]
- Brock N., Pohl J., Stekar J. Studies on the urotoxicity of oxazaphosphorine cytostatics and its prevention. 2. Comparative study on the uroprotective efficacy of thiols and other sulfur compounds. Eur J Cancer Clin Oncol. 1981 Nov;17(11):1155–1163. [PubMed] [Google Scholar]
- Cantwell B. M., Harris A. L., Bozzino J. M. Experience with 24-h infusions of ifosfamide/mesna in small cell lung cancer. Cancer Chemother Pharmacol. 1986;18 (Suppl 2):S29–S29. doi: 10.1007/BF00647447. [DOI] [PubMed] [Google Scholar]
- Cerny T., Margison J. M., Thatcher N., Wilkinson P. M. Bioavailability of ifosfamide in patients with bronchial carcinoma. Cancer Chemother Pharmacol. 1986;18(3):261–264. doi: 10.1007/BF00273399. [DOI] [PubMed] [Google Scholar]
- Creaven P. J., Allen L. M., Alford D. A., Cohen M. H. Clinical pharmacology of isophosphamide. Clin Pharmacol Ther. 1974 Jul;16(1):77–86. doi: 10.1002/cpt1974161part177. [DOI] [PubMed] [Google Scholar]
- Creaven P. J., Allen L. M., Cohen M. H., Nelson R. L. Studies on the clinical pharmacology and toxicology of isophosphamide (NSC-109724). Cancer Treat Rep. 1976 Apr;60(4):445–449. [PubMed] [Google Scholar]
- Juma F. D., Rogers H. J., Trounce J. R., Bradbrook I. D. Pharmacokinetics of intravenous cyclophosphamide in man, estimated by gas-liquid chromatography. Cancer Chemother Pharmacol. 1978;1(4):229–231. doi: 10.1007/BF00257155. [DOI] [PubMed] [Google Scholar]
- Juma F. D., Rogers H. J., Trounce J. R. Pharmacokinetics of cyclophosphamide and alkylating activity in man after intravenous and oral administration. Br J Clin Pharmacol. 1979 Sep;8(3):209–217. doi: 10.1111/j.1365-2125.1979.tb01004.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lind M. J., Margison J. M., Cerny T., Thatcher N., Wilkinson P. M. Comparative pharmacokinetics and alkylating activity of fractionated intravenous and oral ifosfamide in patients with bronchogenic carcinoma. Cancer Res. 1989 Feb 1;49(3):753–757. [PubMed] [Google Scholar]
- Mouridsen H. T., Faber O., Skovsted L. The metabolism of cyclophosphamide. Dose dependency and the effect of long-term treatment with cyclophosphamide. Cancer. 1976 Feb;37(2):665–670. doi: 10.1002/1097-0142(197602)37:2<665::aid-cncr2820370209>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
- Nelson R. L., Allen L. M., Creaven P. J. Pharmacokinetics of divided-dose ifosfamide. Clin Pharmacol Ther. 1976 Mar;19(3):365–370. doi: 10.1002/cpt1976193365. [DOI] [PubMed] [Google Scholar]
- Pearcey R., Calvert R., Mehta A. Disposition of ifosfamide in patients receiving ifosfamide infusion therapy for the treatment of cervical carcinoma. Cancer Chemother Pharmacol. 1988;22(4):353–355. doi: 10.1007/BF00254245. [DOI] [PubMed] [Google Scholar]
- Piazza E., Cattaneo M. T., Varini M. Pharmacokinetic studies in lung cancer patients. Cancer. 1984 Sep 15;54(6 Suppl):1187–1192. doi: 10.1002/1097-0142(19840915)54:1+<1187::aid-cncr2820541316>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
- Scheef W., Klein H. O., Brock N., Burkert H., Günther U., Hoefer-Janker H., Mitrenga D., Schnitker J., Voigtmann R. Controlled clinical studies with an antidote against the urotoxicity of oxazaphosphorines: preliminary results. Cancer Treat Rep. 1979 Mar;63(3):501–505. [PubMed] [Google Scholar]
- Stuart-Harris R. C., Harper P. G., Parsons C. A., Kaye S. B., Mooney C. A., Gowing N. F., Wiltshaw E. High-dose alkylation therapy using ifosfamide infusion with mesna in the treatment of adult advanced soft-tissue sarcoma. Cancer Chemother Pharmacol. 1983;11(2):69–72. doi: 10.1007/BF00254247. [DOI] [PubMed] [Google Scholar]
- Thatcher N., Anderson H., Smith D. B., Steward W. P., Webb K., Hilton A., Rahman A. Ifosfamide by bolus as treatment for advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 1986;18 (Suppl 2):S30–S33. doi: 10.1007/BF00647448. [DOI] [PubMed] [Google Scholar]
- Wilkinson P. M., O'Neill P. A., Thatcher N., Lucas S. B. Pharmacokinetics of high-dose cyclophosphamide in patients with metastatic bronchogenic carcinoma. Cancer Chemother Pharmacol. 1983;11(3):196–199. doi: 10.1007/BF00254204. [DOI] [PubMed] [Google Scholar]
- Zalupski M., Baker L. H. Ifosfamide. J Natl Cancer Inst. 1988 Jun 15;80(8):556–566. doi: 10.1093/jnci/80.8.556. [DOI] [PubMed] [Google Scholar]
