Pharmacogenomics refers to the general study of all of the many different genes that determine drug behavior while pharmacogenetics refers to the study of inherited differences (variation) in drug metabolism and response. The distinction between the two terms is subtle and the two terms are often used interchangeably.
As part of the Pharmacogenomics Research Unit, the The Laboratory of Drug Disposition and Pharmacogenetics conducts a wide variety of research including the study of genetic and environmental factors that influence the outcome of treatment with psychoactive drugs in children and adolescents as well as adults. Further, current studies are evaluating the influence of genetic factors on the placental passage of medications used during pregnancy. Current studies are directed at identifying specific drug transporters and assessing genetic factors that may influence the transport of psychostimulant and antipsychotic medications that ultimately modulate clinical effects and outcomes.
Drug-drug interactions, herbal supplement-drug interactions, and the effects of age and disease states on drug and metabolite disposition are also areas of focus. Laboratory methodology employed includes the use of cell culture, genetically altered (transgenic) animal studies, and drug assay development using various methods of analysis to support pharmacokinetic studies of drug disposition (drug absorption, distribution, metabolism and elimination) in both humans and animals.
Pharmacogenetic studies are conducted to characterize the genotype and/or phenotype of individual’s drug transporter proteins (e.g. P-glycoprotein) and drug metabolizing enzymes. Clinical investigations are conducted in healthy human volunteers as well as patients. Present funding is through the NIH National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse (NIDA), National Center for Complementary and Alternative Medicine (NCCAM), Office of Dietary Supplements, and the pharmaceutical industry.
Publications Related to Herbal Supplements:
Markowitz JS, DeVane CL. The emerging recognition of herb-drug interactions with a focus on St. John’s wort (Hypericum Perforatum). Psychopharm Bull 2001;35:53-64.
Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang J-S, Chavin KD. Effect of St. John’s wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003;290:1500-4.
Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang J-S, Chavin KD. Multiple-doses of Saw Palmetto (Serenoa repens) did not alter CYP2D6 and CYP3A4 activity in normal volunteers. Clin Pharmacol Ther 2003;74:536-42.
Donovan JL, Chavin KD, DeVane CL, Taylor RM, Wang J-S, Ruan Y, Markowitz JS. Green tea (Camellia sinensis) supplementation does not alter cytochrome P-450 3A4 or 2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:906-8.
Donovan JL, DeVane, CL, Lewis, JG, Chavin KD, Wang J-S, Ruan Y, Chavin KD, Markowitz JS. Effects of an extract of St. John’s wort (Hypericum perforatum L.) on plasma androgen concentrations in healthy men and women: A pilot study. Phytotherapy Res 2005;19:901-906.
Representative Publications Related to Conventional Medications:
Markowitz JS, DeVane CL, Boulton DW, Nahas Z, Risch SC, Diamond F, Patrick KS. Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and alcohol. Drug Metab Dispos 2000;28:620-24.
Markowitz JS, DeVane CL, Malcolm RJ, Gefroh HA, Wang J-S, Zhu, H, Donovan JL. Pharmacokinetics of olanzapine after single dose oral administration of standard tablet versus normal and sublingual administration of an orally disintegrating tablet in normal volunteers. J Clin Pharmacol 2006;46:164-171.
Zhu H-J, Wang J-S, Markowitz JS, Donovan JL, Gibson BB, Gefroh HA, DeVane CL. Characterization of p-glycoprotein inhibition by major cannabinoids from marijuana. J Pharmacol Exp Ther 2006;317:850-857
Zhu H-J, Wang J-S, DeVane CL, Williard RL, Donovan JL,Middaugh LD,Gibson BB,PatrickKS, Markowitz JS. The role of the polymorphic efflux transporter p-glycoprotein on the brain accumulation of d-methylphenidate and d-amphetamine. Drug Metab Dispos Published on line April 18, 2006; doi: 10.1124/dmd.106.009605