Methods for reducing dacarbazine photodegradation and its accompanying venous pain]

The anticancer drug dacarbazine (DTIC) is photosensitive, and the photodegradation product 5-diazoimidazole-4-carboxamide (diazo-IC) induces adverse reactions including local venous pain during intravenous injection. In this study we evaluated the effectiveness of colored shields (orange and red) to protect against photodegradation of DTIC as determined by ascertaining the concentration of diazo-IC. Samples were prepared and stored under four conditions: (1) no shield; (2) covered with an aluminum (opaque) shield; (3) covered with an orange shield; and (4) covered with a red shield. The samples were exposed to natural light for a specified time (0, 30, 60, 120, and 180 min) prior to measuring the concentration of diazo-IC by HPLC. We found that after 180 min, the diazo-IC concentration was 5.7 +/- 0.6 (S.D.) mu g/mL with no shield and 1.9 +/- 0.2 mu g/mL in both colored shield conditions. This production of diazo-IC under the colored shields was suppressed to a level similar to that under the aluminum shield (1.7 +/- 0.2 mu g/mL). We also evaluated the effectiveness of NSAIDs (zaltoprofen, loxoprofen sodium, and diclofenac sodium) administered to mice prior to DTIC treatment on venous pain by counting their stretching and writhing reactions. Premedication with zaltoprofen significantly decreased expression of pain behavior in the DTIC-treated mice. These results suggest that storing DTIC under the protection of an orange or red shield is clinically beneficial because the shield prevents DTIC photodegradation, and that NSAIDs such as zaltoprofen are a promising premedication candidate for pain.