Evaluation of the methemoglobinemia associated with sulofenur.

Abstract

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 be overestimated by co-oximeter measurements but that Sulofenur does produce clinically significant methemoglobinemia in cytochrome b5 reductase deficient patients.

• Authors: D C Molthrop Jr, R H Wheeler, K M Hall, J T Prchal
• Journal: Investigational new drugs (Invest New Drugs) Vol. 12 Issue 2 Pg. 99-102 ( 1994) ISSN: 0167-6997 [Print] United States
• PMID: 7860238 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents
• Sulfonylurea Compounds
• Sulfhemoglobin
• Cytochrome Reductases
• Cytochrome-B(5) Reductase
• sulofenur

Topics

• Antineoplastic Agents (adverse effects)
• Cytochrome Reductases (metabolism)
• Cytochrome-B(5) Reductase (metabolism)
• Humans
• Methemoglobinemia (chemically induced)
• Sulfhemoglobin (metabolism)
• Sulfonylurea Compounds (adverse effects)