PMID- 16248851
OWN - NLM
STAT- MEDLINE
DCOM- 20051130
LR  - 20191026
IS  - 1567-2050 (Print)
IS  - 1567-2050 (Linking)
VI  - 2
IP  - 4
DP  - 2005 Oct
TI  - Anticholinesterase and pharmacokinetic profile of phenserine in healthy elderly 
      human subjects.
PG  - 483-92
AB  - 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.
FAU - Greig, Nigel H
AU  - Greig NH
AD  - Drug Design & Development Section, Laboratory of Neurosciences, National 
      Institute on Aging, National Institutes of Health, Baltimore, MD 21224 USA. 
      Greign@grc.nia.nih.gov
FAU - Ruckle, Jon
AU  - Ruckle J
FAU - Comer, Patrick
AU  - Comer P
FAU - Brownell, Lidia
AU  - Brownell L
FAU - Holloway, Harold W
AU  - Holloway HW
FAU - Flanagan, Douglas R Jr
AU  - Flanagan DR Jr
FAU - Canfield, Craig J
AU  - Canfield CJ
FAU - Burford, Robert G
AU  - Burford RG
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Alzheimer Res
JT  - Current Alzheimer research
JID - 101208441
RN  - 0 (Cholinesterase Inhibitors)
RN  - 9U1VM840SP (Physostigmine)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - SUE285UG3S (phenserine)
SB  - IM
MH  - Acetylcholinesterase/drug effects
MH  - Aged
MH  - Area Under Curve
MH  - Cholinesterase Inhibitors/*adverse effects/*pharmacokinetics
MH  - Erythrocytes/drug effects/enzymology
MH  - Female
MH  - Humans
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Physostigmine/adverse effects/*analogs & derivatives/pharmacokinetics
EDAT- 2005/10/27 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/10/27 09:00
PHST- 2005/10/27 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/10/27 09:00 [entrez]
AID - 10.2174/156720505774330564 [doi]
PST - ppublish
SO  - Curr Alzheimer Res. 2005 Oct;2(4):483-92. doi: 10.2174/156720505774330564.