Summary
A new class of antineoplastic agents, the diarylsulfonylureas entered clinical trials with the testing of Sulofenur (LY186641). Phase I trials and preclinical studies showed the dose limiting toxicity to be methemoglobinemia. We studied the incidence of methemoglobinemia, sulfhemoglobinemia 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 were noted. One patient with symptomatic methemoglobinemia had enzyme levels and family history consistent with a heterozygous state for a cytochrome b5 reductase deficiency.
We conclude that the clinical incidence of methemoglobinemia will de overestimated by co-oximeter measurements but that Sulofenur does produce clinically significant methemoglobinemia in cytochrome b5 reductase deficient patients.
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Molthrop, D.C., Wheeler, R.H., Hall, K.M. et al. Evaluation of the methemoglobinemia associated with Sulofenur. Invest New Drugs 12, 99–102 (1994). https://doi.org/10.1007/BF00874438
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DOI: https://doi.org/10.1007/BF00874438