Anticholinesterase and pharmacokinetic profile of phenserine in healthy elderly human subjects.

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Greig NH, Ruckle J, Comer P, Brownell L, Holloway HW, Flanagan DR Jr, Canfield CJ, Burford RG

Anticholinesterase and pharmacokinetic profile of phenserine in healthy elderly human subjects.

Curr Alzheimer Res. 2005 Oct;2(4):483-92.

PubMed ID

16248851 [ View in PubMed

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Abstract

OBJECTIVE: To evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics (PD) of the acetyl-selective anticholinesterase, phenserine tartrate, in healthy elderly subjects. METHODS: 32 healthy elderly volunteers received single oral doses of phenserine tartrate (5-20 mg). Physical and vital signs were monitored over the ensuing 24 hours. Analyses were performed on plasma samples to determine PK, and PD were assessed using an erythrocyte acetylcholinesterase (AChE) inhibition assay. RESULTS: No serious adverse events (AEs) occurred; the most common were headache and vomiting. The MTD of phenserine tartrate was 10 mg. The Cmax and AUC(0-24) of phenserine increased with dose, but neither were dose-proportional. Subjects receiving 10 mg of phenserine tartrate had a Cmax of 1.95 ng/mL at 1.5 hours, and the mean peak inhibition (Imax) of AChE was 26% (range: 18-34%) at 1.75 hours (tImax) following dosing. The half-life of AChE inhibition (tI1/2) was 11 hours. Evaluation of PK/PD relationships suggested a linear correlation between plasma phenserine concentration and AChE inhibition in the blood. CONCLUSIONS: Phenserine tartrate was safe and well tolerated when administered as a single oral dose of either 5 mg or 10 mg. An increase in the severity and frequency of AEs occurred at the 20 mg dose level.

DrugBank Data that Cites this Article

Drugs

Phenserine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Phenserine	Acetylcholinesterase	Protein	Humans	Unknown	Not Available	Details