John S Markowitz, Pharm.D., BCPP

Dr. Markowitz received his BS in Biology from Memphis State University, and his Doctorate in Pharmacy (Pharm.D.) from the University of Tennessee Center for the Health Sciences (UTCHS). He completed an ASHP-accredited specialty residency in Psychiatric Pharmacy Practice, also at UTCHS. Following his education and training, Dr. Markowitz served for a decade as a Clinical Specialist in Psychiatry, and eventually Clinical Coordinator within the Institute of Psychiatry at the Medical University of South Carolina (MUSC) in Charleston, South Carolina. He eventually transitioned from clinician to a primary faculty research position in the MUSC College of Pharmacy’s Department of Pharmaceutical & Biomedical Sciences with a dual appointment in the Department of Psychiatry and Behavioral Sciences where he had remained prior to joining the UF College of Pharmacy in 2009. Dr. Markowitz has been credentialed by the Board of Pharmaceutical Specialties in Psychiatric Pharmacy (BCPP) since 1997 and is a founding member of the College of Psychiatric and Neurologic Pharmacists (CPNP).

• Board Certified Psychiatric Pharmacist (BCPP) # 496267

  Board of Pharmaceutical Specialties (BPS)
• Registered Pharmacist

  Board of Pharmacy-State of Florida

Dr. Markowitz’s research program has encompassed both in vitro and in vivo investigations including normal volunteer pharmacokinetic studies directed at the assessment of drug-drug interactions in psychiatric pharmacy, botanical-drug interactions, as well as their associated clinical effects. More recently, the research program has focused on variability in drug metabolism, disposition, and therapeutic response as a consequence of genetic variability influencing both drug transporters and hepatic enzymes. The serine esterase carboxylesterase 1 (CES1) is of particular interest. Dr. Markowitz has received research support from both the pharmaceutical industry and the National Institutes of Health (NIH) serving as the principal investigator of research grants funded by an array of institutes including NCCAM, NIDA, NIAID, and most recently NICHD. He has authored or co-authored 165 peer-reviewed papers topics in journals such as Clinical Pharmacology & Therapeutics, JAMA, Journal of Clinical Psychopharmacology, J Neurochemistry, Drug Metabolism and Disposition, JPET, and Neuropsychopharmacology.

MARKOWITZ LABORATORY (MSB0445, P Wing, RM P2-32)

The research focus of the Markowitz lab encompasses two primary areas that are somewhat intertwined which relate to individual variability in drug response. These two areas are i) Drug Metabolism and Disposition and ii) Pharmacogenomics. The primary therapeutic area receiving focus from both research themes are neuropsychiatric medications.

Drug Metabolism and Disposition The importance of absorption, distribution, metabolism, and excretion – toxicity (ADMET) of therapeutic agents extends far beyond the initial research and development in Phases I, II, and III within the pharmaceutical industry and well into the post-marketing period. It is this period in which drug exposures go from perhaps less than 5000 individuals to millions of exposures annually. Our program focuses on a variety of environmental factors which govern drug response, tolerability, adverse effects and toxicity. These factors include drug-drug interactions, alcohol-drug interactions, botanical-drug interactions, smoking, and assessment of novel pharmaceutical formulations. Our laboratory relies on a number of investigative approaches including cell culture and novel cell line development for in vitro studies, in vivo animal models, ex vivo approaches, and healthy volunteer pharmacokinetic studies. Further, we also have experience in developing novel LC-MS/MS assays for the detection and quantitation of parent drug and metabolites as well as phytoconstituents of botanical extracts.

Pharmacogenomics of Drug Metabolizing Enzymes and Drug Transporters Genetic mutations can significantly influence the activity and expression of drug metabolizing enzymes (DMEs) as well as the activity of drug transporters. These influences can significantly alter drug absorption and metabolism and lead to adverse events and toxicities, or therapeutic failure. Moreover, prodrug formulations dependent on DMEs for activation may become ineffective in certain circumstances. Our research group discovered and characterized the carboxylesterase 1 (CES1) gene variant, p.Gly143Glu which is arguably the most clinically significant CES1 variant recognized today. The presence of this variant results in markedly reduced activity of the CES1 enzyme, the major hepatic hydrolase responsible for hydrolyzing (inactivating or activating) a wide variety of therapeutic agents. A currently funded research project (1 R01 HD093612-01A1, NICHD) permits us to study the influence of genetic variation in CES1 on the metabolism and response to the psychostimulant, and CES1 substrate, methylphenidate in children with Attention-deficit/hyperactivity disorder (ADHD) A further research theme has been the assessment of the interaction of CNS compounds with the efflux transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) as well as the Organic Cation Transporters (OCT) 1-3 utilizing both cell lines as well as knock-out animal models. As discussed, my lab will perform the analysis of drug concentrations collected from proposed animal experiments, and perform pharmacokinetic analyses.

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