Clinical Neuropharmacology Research Focus

Our analytical lab is routinely involved in development and implementation of high throughput assays for a variety of drugs including but not limited to, anti-epileptic drugs, cannabidols, and anti-depressants. Our group is currently the core pharmacokinetic laboratory for a national multi-center study MONEAD that is studying pharmacokinetic changes during and post pregnancy. Analysis for most studies is done using Shimadzu LCMS 2020 single quadrupole system and Shimadzu LCMS/MS 8050 triple quadrupole system which allow for the sensitivity needed for nearly any project. We also have experience in size exclusion chromatography using LC-UV detection. We are also well versed in sample preparation techniques. We have researched and developed assays to fit many a project demands.

• Drug assays developed in our can be viewed here.

• Read about our lab capabilities here.

Our lab specializes in pharmacokinetic studies in preclinical and clinical settings. We perform a wide range of studies including ADME studies, bioavailability, bioequivalence, drug interaction studies, and liver microsomal studies to name a few.

We have a special focus on antiepileptic drugs and their pharmacokinetics. Our research group has created stable isotope labeled anti-seizure medications enabling study of patients while at steady-state dosing through simultaneous measurement of drugs given by different routes including intravenous, oral, and intramuscular.

We also focus on special populations such as pregnant women with epilepsy and elderly where the pharmacokinetics of antiepileptic drugs are altered due to physiological changes.

Our research group is known for expertise with pharmacometric modeling to answer pertinent clinical questions. We are a "Center for Excellence" with Pharsight that is based on the modeling expertise and reputation of our research group. We have a very unique and translational group of researchers and our expertise translates across several fields including pharmacology, neuroscience, and linguistics.

Pharmacometrics involves the use of pharmaco-statistical models to quantitate the effect of different factors on a drug's pharmacokinetics. It provides a tool that can estimate pharmacokinetic parameters and quantitate the contribution of covariates as well as the estimate the variability around each estimated parameter. It is especially useful when only sparse sampling is available as seen in particular patient populations including children and the elderly or pregnant women with epilepsy.

Our in-silico lab is equipped with several 64-bit workstation and server grade computers along with population pharmacokinetic modeling softwares such as NONMEM, PDxPop, Pirana and Phoenix NLME.

Our lab also works in the field of pharmacogenomics to understand how a person's genome would alter antiepileptic drug pharmacokinetics and pharmacodynamics.

Drug exposure can be affected by many factors including the presence of single nucleatide polymorphisms (SNPs) in metabolic enzymes. Anti-seizure medications are known to be extensively metabolized by the liver and can involve the cytochrome P450 isoenzyme system. The presence of particular SNPs in the coding regions of such enzyme systems may determine the disposition of a drug and can explain inter-patient variability in clinical response. Our research has identified SNPs that explain a portion of the variability in patient populations.

We also specialize in the exploration of cognitive effects of medications as well as using drugs as probes to explore the mechanisms involved in cognitive changes due to the presence of medications. Our studies have led to the creation of the Center for Clinical and Cognitive Neuropharmacology at the University of Minnesota for which I am a founding member.