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.
Clinical Pharmacokinetics Unit, Pharmacia & Upjohn, Inc., Kalamazoo, Michigan 49007, USA.
J C
JC
Fleishaker
G R
GR
Peters
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