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Fractionated ifosfamide therapy produces a time‐dependent increase in ifosfamide metabolism.
Author(s) -
Lewis LD,
Fitzgerald DL,
Harper PG,
Rogers HJ
Publication year - 1990
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1990.tb03842.x
Subject(s) - ifosfamide , nitrogen mustard , pharmacokinetics , volume of distribution , urine , chemistry , concomitant , medicine , urology , half life , pharmacology , chemotherapy , cyclophosphamide , etoposide
1. Fifteen patients received 1.5 g m‐2 of ifosfamide intravenously over 0.5 h every day for 5 days. Twenty‐one courses of treatment were studied. Plasma was assayed for ifosfamide by gas liquid chromatography and plasma alkylating activity was measured using the nitrobenzylpyridine (NBP) reaction. 2. A pharmacokinetic analysis revealed a significant decrease in the median (range) elimination half‐ life of ifosfamide from 7.2 (2.8‐14.2) h on day 1 to 4.6 (2.3‐7.7) h on day 5 (P less than 0.001, Wilcoxon's test) with a concomitant significant increase in the median (range) clearance from 66 (31‐148) ml min‐1 on day 1 to 115 (52‐381) ml min‐1 on day 5 (P less than 0.001). There was no significant change in the volume of distribution on day 5 compared with day 1. 3. There was a highly significant 223% increase in the median (range) plasma nitrobenzylpyridine alkylating activity area under the curve on day 1 from 16 (0.6‐105) nmol nor nitrogen mustard equivalents ml‐1 h to 52 (13‐238) nmol nor nitrogen mustard equivalents ml‐1 h on day 5. 4. During five courses of treatment (in five patients in the group) 24 h urine samples were collected on days 1 and 5. The median (range) renal clearance of ifosfamide on day 1 was 6.8 (1.3‐16.2) ml min‐1 compared with 5.7 (1.3‐ 15.3) ml min‐1 on day 5. This difference was not significant. The median (range) metabolic clearance of ifosfamide in these five patients on day 1 was 78.6 (39.9‐141.2) ml min‐1 and 132.6 (54.6‐149.5) ml min‐1 on day 5.(ABSTRACT TRUNCATED AT 250 WORDS)