Clinical pharmacokinetics of (NPAz2)2NSOAz: 'SOAz'.
Pharmacokinetic studies of 1,3,3,5,5 pentakis (aziridino)-1 lambda 6,2,4,6,3 lambda 5,5 lambda 5 thiatriazadiphosphorine-1-oxide ('SOAz'), a new antineoplastic agent containing an inorganic ring system and five aziridino groups, were performed in six patients who took part in a phase I clinical trial of the agent. The drug was administered as a rapid IV infusion. Serum decay curves could be fitted to an open two-compartment model of drug disappearance. After a short initial phase with a t 1/2 (+/- SD) of 7.8 +/- 4.2 min a terminal phase with a dose-independent half-life of 203 +/- 17 min occurred. The coefficient of apparent distribution was 0.71 +/- 0.13. The renal clearance was 75 +/- 11 ml/min and the total body clearance 162 +/- 23 ml/min. A percentage of 46.5 +/- 6.6 of the administered drug could be recovered unchanged in the urine within 24 h. It is concluded that in view of concentrations known to be effective in vitro, administration in large single doses may be advantageous. Dose adjustments should be made for patients with impaired renal function.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D001389:Azirines / Q000378:metabolism* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D000970:Antineoplastic Agents; D001389:Azirines; C035161:pentazirinocyclodiphosphathiazene