EVALUATION OF THE METHEMOGLOBINEMIA ASSOCIATED WITH SULOFENUR

A new class of antineoplastic agents, the diarylsulfonylureas entered clinical trials with the testing of Sulofenur (LY186641). Phase I tria ls and preclinical studies showed the dose limiting toxicity to be met hemoglobinemia. We studied the incidence of methemoglobinemia, sulfhem oglobinemia and cytochrome b5 reductase deficiency in nine consecutive patients enrolled in a phase II trials using Sulofenur. The specific Malloy method as well as clinically standard co-oximeter measurements were used to determine methemoglobin levels and marked discrepancies w ere noted. One patient with symptomatic methemoglobinemia had enzyme l evels and family history consistent with a heterozygous state for a cy tochrome b5 reductase deficiency. We conclude that the clinical incide nce of methemoglobinemia will de overestimated by co-oximeter measurem ents but that Sulofenur does produce clinically significant methemoglo binemia in cytochrome b5 reductase deficient patients.