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Intradermal carboplatin and ifosfamide extravasation in the mouse
1School of Pharmacy, University of Wisconsin-Madison 53706.
Background:
Carboplatin and ifosfamide are new antineoplastic agents with vesicant properties that have not been determined. Vesicant activity was investigated in Balb-c mice by administering carboplatin or ifosfamide intradermally in clinically relevant concentrations.
Methods:
Carboplatin concentrations tested were 15, 10, and 1 mg/ml; those of ifosfamide were 50, 20, and 1 mg/ml. Five female mice were tested with each concentration; and five animals were used as controls and received only saline.
Results:
Carboplatin concentrations of 15 mg/ml and 10 mg/ml produced mean peak ulcer areas of 10 square millimeters (mm2) and 21 mm2 within 2-3 days of injection, respectively. The 1 mg/ml carboplatin injection was not associated with any ulcer formation. Ifosfamide at 50 mg/ml induced skin ulcerations in four of five mice, with maximal effect (19.6 mm2) by 1-2 days. Lower concentrations of ifosfamide produced no ulcerations. All ulcerative lesions healed completely within 21 days.
Conclusions:
These results suggest that extravasation of carboplatin at concentrations of greater than or equal to 10 mg/ml or ifosfamide at concentrations of greater than or equal to 50 mg/ml is likely to cause ulcers in humans.