Pharmacokinetics of dexamphetamine in acute stroke.

Pharmacokinetics of dexamphetamine was studied in 26 patients with cerebral infarct, aged 37 to 84 years. Capsules were administered orally twice daily (at 8 am and 12 am) in three doses (2.5 mg, 5 mg, and 10 mg) for 5 consecutive days (day 1 to day 5). Blood samples were collected immediately before and 1, 2, 3, 4, 5, 6, 7, 8, and 9 hours after first administration on day 1 and before, and 4 and 8 hours after administration on days 2 through 5. The dose normalized area under the plasma concentration time curve, AUC/mg/kg, was only correlated with s-creatinine (P = 0.013) but not with age, sex, body mass index, neurologic prognosis, or dose (mg/kg), as established by multiple stepwise linear regression. The median terminal half life time was 14.3 hours (inter quartile range, IQR: 11.9-6.9), 13.1 (IQR: 10.8-15.9) and 14.0 (IQR: 7.4-16.4) in the 2.5 mg, 5 mg, and 10 mg groups, respectively. The median maximal plasma concentration (Cmax) was 6.6 ng/mL (IQR: 5.1-7.0), 11.6 (IQR: 7.8-12.8), and 16.9 (IQR: 14.9-20.2) in the 2.5 mg, 5 mg, and the 10 mg groups, respectively. Differences in Cmax between the 2.5 mg and 10 mg group were significant (P < 0.001). The median time to Cmax (Tmax) was 1.83 hours (IQR: 1.79-3.94), 2.59 (IQR: 1.32-3.83), and 3.86 (IQR: 1.82-5.77) in the 2.5, 5, and 10 mg groups, respectively. In the present patient population, a predetermined AUC value can be obtained by a dosing regimen of dexamphetamine based on body weight (ie, mg/kg), with precautions for patients with elevated s-creatinine.