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  • Title: Steady-state pharmacokinetics of tacrine in patients with Alzheimer's disease.
    Author: Cutler NR, Sedman AJ, Prior P, Underwood BA, Selen A, Balogh L, Kinkel AW, Gracon SI, Gamzu ER.
    Journal: Psychopharmacol Bull; 1990; 26(2):231-4. PubMed ID: 2236461.
    Abstract:
    Neurochemical studies of Alzheimer's disease (AD) suggest deficiencies in the cholinergic system. We evaluated the steady-state pharmacokinetics of tacrine (Cognex), an oral cholinesterase inhibitor, in 12 patients with AD. Patients sequentially received nine doses of 10 mg, 20 mg, and 30 mg of tacrine every 6 hours. Blood samples were collected until 24 hours after the final dose. Plasma tacrine concentrations were measured using a validated high-performance liquid chromatographic method. Mean maximum plasma concentrations (Cmax) were 5.1 ng/ml, 20.7 ng/ml, and 33.9 ng/ml following administration of 10 mg, 20 mg, and 30 mg doses, respectively. Corresponding mean values for steady-state area under the curve (AUC) were 19.7 ng/ml, 82.9 ng/ml, and 139 ng/ml.hr. Dose-normalized Cmax and AUC values after administration of the 20 mg and 30 mg doses of tacrine were comparable to each other but were significantly greater (p less than .05) than those after the 10 mg doses. The apparent elimination half-life was approximately 3.4 hours for all dosing regimens. Dose-dependent increases in Cmax and AUC values in patients with AD were similar to those previously reported in normal volunteers. The mechanism of the nonlinearity in tacrine pharmacokinetics is unknown.
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