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 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.
Molthrop
D C
DC
Department of Medicine, Cooper Green Hospital, Birmingham, AL.
Wheeler
R H
RH
Hall
K M
KM
Prchal
J T
JT
D000970:Antineoplastic Agents / Q000009:adverse effects*; D003579:Cytochrome Reductases / Q000378:metabolism; D042966:Cytochrome-B(5) Reductase / Q000378:metabolism; D006801:Humans; D008708:Methemoglobinemia / Q000139:chemically induced*; D013435:Sulfhemoglobin / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000009:adverse effects*
D000970:Antineoplastic Agents; D013453:Sulfonylurea Compounds; D013435:Sulfhemoglobin; D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase; C058179:sulofenur