Clinical pharmacokinetics of I-123-IAZA in healthy volunteers

I-123-labelled iodoazomycin arabinoside (I-123-IAZA) is an experimental rad iopharmaceutical that has been shown to have clinical utility for imaging r egional tissue hypoxia. We report the clinical pharmacokinetics of IAZA, th e radiopharmacokinetics of I-123-IAZA and total radioactivity kinetics afte r injection of I-123-IAZA. Six healthy volunteers each received an intraven ous bolus injection of 185 MBq of I-123-IAZA. Thirteen blood samples and a cumulative urine sample were collected over 28 h from each subject. A two-c ompartment open model best described the disposition characteristics of all three chemical components, with terminal phase half-lives of 179 +/- 24, 2 32 +/- 41 and 294 +/- 27 min for I-123-IAZA, IAZA and total radioactivity, respectively. I-123-IAZA had a steady-state volume of distribution (V-ss) o f 0.716 +/- 0.088 l.kg(-1) and a systemic clearance (Cl-s) of 239 +/- 48 ml .min(-1). Radioactive decay was responsible for about 37% of clearance; of the remaining radioactivity, about 92% was eliminated renally. Only about 1 2% of I-123-IAZA was eliminated unchanged in urine, indicating that renal e xcretion was the major route of elimination for the radioactive metabolites rather than for I-123-IAZA itself. The effective half-lives of I-123-IAZA and total radioactivity reported here are considerably shorter than previou sly estimated. Our results confirm that I-123-IAZA has appropriate pharmaco kinetic and radiopharmacokinetic properties to support clinical hypoxia ima ging. ((C) 1999 Lippincott Williams & Wilkins).