Pharmacokinetics of tirilazad and U-89678 in ischemic stroke patients receiving a loading regimen and maintenance regimen of 10 mg/kg/day of tirilazad.
The pharmacokinetics of tirilazad mesylate and its active reduced metabolite, U-89678, were evaluated in ischemic stroke patients receiving 2.5 mg/kg tirilazad every 3 hours for the first 12 hours of dosing followed by 2.5 mg/kg every 6 hours for a total of 22 doses (5 days). Trough and serial samples drawn during the 6 hours after administration of the last dose were analyzed for plasma levels of tirilazad and U-89678 by means of high-performance liquid chromatography. Complete concentration-time profiles were available for 20 patients, including 12 men (mean age, 68.0 years) and 8 women (mean age, 75.0 years). Trough concentrations of tirilazad and U-89678 were consistent with the loading regimen used. The mean area under the concentration-time curve from time 0 to 6 hours (AUC0-6) of tirilazad was 8181 +/- 2398 ng.hr/mL in men and 8135 +/- 3671 ng.hr/mL in women. The mean AUC0-6 of U-89678 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 pharmacokinetics of U-89678 but little effect on the pharmacokinetics of tirilazad in elderly ischemic stroke patients. These observations are consistent with previous findings in healthy young and elderly subjects.
Fleishaker
J C
JC
Clinical Pharmacokinetics Unit, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49007, USA.
Peters
G R
GR
D000368:Aged; D019540:Area Under Curve; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011281:Pregnatrienes / Q000008:administration & dosage / Q000493:pharmacokinetics*
D018696:Neuroprotective Agents; D011281:Pregnatrienes; C087053:U 89678; C053355:tirilazad