Investigating the African Green Monkey as a Preclinical Model for Pharmacokinetics: Age and Sex Influences on Drug Metabolism

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In this project, we investigate the pharmacokinetic differences in drugs metabolized by cytochrome P450 (CYP) enzymes in African green monkeys, focusing on the influence of age and sex on metabolism. Utilizing in vivo data, including drug concentrations in plasma and cerebrospinal fluid (CSF), we analyze the pharmacokinetics of the following drugs:

 

1) Nicotine/Cotinine (CYP2A6), an approved smoking cessation aid (DrugBank ID: DB00184),

 

2) Dextromethorphan/Dextrophan (CYP2D6), an approved antitussive agent (DrugBank ID: DB00514),

 

3) Bupropion/Hydroxybupropion (CYP2B6), an approved treatment for major depressive disorder (MDD), seasonal affective disorder (SAD), and smoking cessation (DrugBank ID: DB01156),

 

4) and Chlorzoxazone, a muscle relaxant (DrugBank ID: DB00356).

 

To enhance our understanding of interspecies variations and their influence on drug metabolism, we are developing a population pharmacokinetic (PopPK) model.  (Supervised by: Dr. Rachel Tyndale) ​​​​​​​