PHARMACOKINETICS OF TIRILAZAD AND U-89678 IN ISCHEMIC STROKE PATIENTSRECEIVING A LOADING REGIMEN AND MAINTENANCE REGIMEN OF 10 MG KG/DAY OF TIRILAZAD/

The pharmacokinetics of tirilazad mesylate and its active reduced meta bolite, U-89678, were evaluated in ischemic stroke patients receiving 2.5 mg/kg tirilazad every 3 hours for the first 12 hours of dosing fol lowed by 2.5 mg/kg every 6 hours for a total of 22 doses (5 days). Tro ugh and serial samples drown during the 6 hours after administration o f the last dose were analyzed for plasma levels of tirilazad and U-896 78 by means of highperformance liquid chromatography. Complete concent ration-time profiles were available for 20 patients, including 12 men (mean age, 68.0 years) and 8 women (mean age, 75.0 years). Trough conc entrations of tirilazad and U-89678 were consistent with the loading r egimen used. The mean area under the concentration-time curve from tim e 0 to 6 hours (AUC(0-6)) of tirilazad was 8181 +/- 2398 ng . hr/mL in men and 8135 +/- 13671 ng . hr/mL in women. The mean AUC(0-6) of U-89 678 was 2761 +/- 1834 ng . hr/mL in men and 1477 +/- 903 ng . hr/ml in women. These results show that gender has a modest effect on the phar macokinetics of U-89678 but little effect on the pharmacokinetics of t irilazad in elderly ischemic stroke patients, These observations are c onsistent with previous findings in healthy young and elderly subjects .