Clinical pharmacology of IMPY by radioimmunoassay.
A radioimmunoassay for IMPY has been developed using [3H]acetyl-IMPY and antibody induced by immunizing rabbits with succinyl-IMPY bovine serum albumin conjugates. The method was reproducible and sensitive at a dose of 0.2 microgram/ml. The cross-reactivities of IMPY and IMPY derivatives with the antibody were compared. Using this radioimmunoassay, clinical pharmacology was performed in cancer patients during phase I trials. Following 30-60-minute iv infusions of IMPY (450-1500 mg/m2/day for 5 days), the drug disappeared rapidly from plasma with an initial half-life of less than 10 minutes and second half-life of 4 hours. The half-lives are not affected by minimally abnormal hepatic function and are not dose-related. The apparent volume of distribution was approximately 125 ml/kg. The results obtained on Day 5 were essentially the same as those obtained on Day 1. IMPY was also detected in glioblastoma, brain, and temporalis muscle when the drug (500 mg/m2) was infused iv 4-5 hours before surgery. The tissue drug levels were comparable to or higher than those of plasma. The drug was also measurable in kidney and liver tissues obtained 4 hours after death in a patient who died 21 hours after iv infusion of IMPY at a dose of 1500 mg/m2/day for 3 days.
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000032:analysis*; D003429:Cross Reactions; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods*; D012015:Reference Standards
D000970:Antineoplastic Agents; D011720:Pyrazoles; C026262:imidazopyrazole