TY - JOUR
T1 - Pharmacokinetics of cotinine in rats
T2 - A potential therapeutic agent for disorders of cognitive function
AU - Li, Pei
AU - Beck, Wayne D.
AU - Callahan, Patrick M.
AU - Terry, Alvin V.
AU - Bartlett, Michael G.
N1 - Funding Information:
The authors would like to acknowledge the National Institute on Aging ( AG029617 ) and the National Institute on Drug Abuse ( DA029127 ) for funding.
Publisher Copyright:
© 2014 Institute of Pharmacology, Polish Academy of Sciences Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
PY - 2015/6
Y1 - 2015/6
N2 - Background Attention has been paid to cotinine (COT), one of the major metabolites of nicotine (NIC), for its pro-cognitive effects and potential therapeutic activities against Alzheimer's disease (AD) and other types of cognitive impairment. In order to facilitate pharmacological and toxicological studies on COT for its pro-cognitive activities, we conducted a pharmacokinetic (PK) study of COT in rats, providing important oral and intravenously (IV) PK information. Methods In this study, plasma samples were obtained up to 48 h after COT was dosed to rats orally and IV at a dose of 3 mg/kg. Plasma samples were prepared and analyzed using a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalytical method, providing concentration profiles of COT and metabolites after oral and IV administrations. Results The data were fitted into a one-compartment model and a two-compartment model for the oral and IV groups, respectively, providing important PK information for COT including PK profiles, half-life, clearance and bioavailability. The results suggested fast absorption, slow elimination and high bioavailability of COT in rats. Conclusions Several important facts about the PK properties in rats suggested COT could be a potential pro-cognitive agent. Information about the pharmacokinetics of COT in rats revealed in this study is of great importance for the future studies on COT or potential COT analogs as agents for improving cognition.
AB - Background Attention has been paid to cotinine (COT), one of the major metabolites of nicotine (NIC), for its pro-cognitive effects and potential therapeutic activities against Alzheimer's disease (AD) and other types of cognitive impairment. In order to facilitate pharmacological and toxicological studies on COT for its pro-cognitive activities, we conducted a pharmacokinetic (PK) study of COT in rats, providing important oral and intravenously (IV) PK information. Methods In this study, plasma samples were obtained up to 48 h after COT was dosed to rats orally and IV at a dose of 3 mg/kg. Plasma samples were prepared and analyzed using a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalytical method, providing concentration profiles of COT and metabolites after oral and IV administrations. Results The data were fitted into a one-compartment model and a two-compartment model for the oral and IV groups, respectively, providing important PK information for COT including PK profiles, half-life, clearance and bioavailability. The results suggested fast absorption, slow elimination and high bioavailability of COT in rats. Conclusions Several important facts about the PK properties in rats suggested COT could be a potential pro-cognitive agent. Information about the pharmacokinetics of COT in rats revealed in this study is of great importance for the future studies on COT or potential COT analogs as agents for improving cognition.
KW - Cognition
KW - Cotinine
KW - Hydrophilic interaction chromatography
KW - Pharmacokinetics
KW - Tandem mass spectrometry
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U2 - 10.1016/j.pharep.2014.12.004
DO - 10.1016/j.pharep.2014.12.004
M3 - Article
C2 - 25933960
AN - SCOPUS:84961343830
SN - 1734-1140
VL - 67
SP - 494
EP - 500
JO - Pharmacological Reports
JF - Pharmacological Reports
IS - 3
ER -