Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2,3 dihydro-IH-imidazo (1,2-b) pyrazole (IMPY) is a potential chemotherapeutic agent known to inhibit cellular DNA synthesis by blocking ribonucleotide reductase. During Phase I clinical studies with IMPY, patients developed a dose dependent hemolytic anemia possibly secondary to oxidant damage to the RBC. We therefore studied the effect of IMPY on the metabolism of human RBC's in vitro. IMPY, in clinically achievable concentrations, stimulated the hexose monophosphate shunt (HMPS) pathway of RBC's. This was associated with the generation of reactive oxygen species as demonstrated by the glutathione (GSH) instability and enhanced formate oxidation of RBC's incubated with the drug. In addition, the GSH concentration of the red cells of a patient fell during a continuous infusion of IMPY. These effects of IMPY on red cell metabolism in vitro and in vivo are similar to those of drugs known to cause oxidative damage to this cell. The capacity of IMPY to act as an oxidant could explain the hemolytic anemia seen in patients receiving this drug.
 ...
PMID:Effect of 2,3-dihydro-1H-imidazo [1,2-b]pyrazole (IMPY) on the metabolism of human red cells. 667 73

IMPY was given to 25 patients with advanced cancer on a twice weekly schedule in escalating doses from 165 to 3000 mg/m2. Nausea, vomiting, fatigue, generalized weakness, and decreases in performance status were dose-limiting. In one patient treated at a dose of 3000 mg/m2 for three doses, hemolytic anemia resulted, with a 6-g/dl decrease in hemoglobin. No tumor regression occurred. A reasonable starting dose for phase II studies is 1200 mg/m2 twice weekly for 3 weeks, with planned rapid escalation to 1800 mg/m2 in patients tolerating the lower dose level.
 ...
PMID:Phase I evaluation of IMPY in a twice weekly schedule. 723 64