John Markowitz, Pharm.D., BCPP
.	Associate Professor Department of Pharmaceutical Sciences Certifications: BCPP Office: Children's Research Institute (CRI), RM 412 PO Box: 250514 Office Phone: 843-792--0172 Research Area:  Pharmacogenetics, Psychopharmacy, Natural Products E-mail: markowij@musc.edu CV

Description of Research Program
Research interests include the study of genetic and environmental factors that influence the outcome of treatment with psychoactive drugs. Current studies are directed at identifying specific drug transporters and assessing genetic factors which may influence the transport of psychostimulant and antipsychotic medications which ultimately modulate clinical effects and outcomes. Drug-drug interactions, botanical-drug interactions, and the effects of age and disease states on drug and metabolite disposition are also areas of focus. Laboratory methodology employed includes cell culture, transgenic animal studies, and drug assay development using HPLC to support pharmacokinetic studies of drug disposition (drug absorption, distribution, metabolism and elimination) in both humans and animals. Pharmacogenetic studies (the effects of inheritance on drug disposition) 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. 

Selected Publications Related to Psychotropic Medications

Markowitz JS, Logan BK, Diamond F, Patrick KS. Detection of the novel metabolite ethylphenidate following methylphenidate overdose with alcohol co-ingestion. J Clin Psychopharmacol 1999;19:362-6.

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;28:620-624.

Boulton DW, DeVane CL, Liston HL, Markowitz JS.  P-glycoprotein specificity for atypical and conventional antipsychotics as determined by their adenosine  triphosphatase (ATPase) activity. Life Sci 2002;163-9.

Markowitz JS, Straughn AB, Patrick KS, DeVane CL, Pestreich L, Lee J, Wang Y, Muniz R. Pharmacokinetics of methylphenidate after oral administration of two modified-release formulations in healthy adults. Clin Pharmacokinet 2003;42:393-401.

Wang J-S, Taylor R, Ruan Y, Donovan JL, Markowitz JS, DeVane CL. Olanzapine penetration into brain is greater in transgenic Mdr1a P-glycoprotein deficient mice than FVB1 (wild type) animals. Neuropsychopharmacology 2004;29:551-7.

Wang J-S, Taylor R, Ruan Y, Donovan JL, Markowitz JS, DeVane CL. The brain entry of risperidone and 9-hydroxyrisperidone are greatly limited by P-glycoprotein. Int J Neuropsychopharmacology 2004;7:1-5.

Wang JS, Markowitz JS, Donovan JL, DeVane CL. P-glycoprotein does not actively transport nicotine and cotinine. Addiction Biology 2005;10:127-9.

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 (in press, 2006).

Selected Publications Related to Natural Products

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, DeVane CL, Chavin KD, Taylor RM, Ruan Y, Donovan JL. Effects of garlic (Allium sativum L) supplementation on cytochrome P450 2D6 and 3A4 activity in normal volunteers. Clin Pharmacol Ther 2003;74:170-7.

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.

Markowitz JS, Donovan JL, DeVane CL, Sipkes L, Chavin KD. Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers J Clin Psychopharmacol 2003;23:676-8.

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, Chavin KD, Wang J-S, Gibson BB, Gefroh HA, Markowitz JS. Multiple nighttime doses of valerian (Valeriana officinalis) had minimal effects on CYP 3A4 activity and no effect on CYP 2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:1333-6.

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.

Donovan JL, DeVane CL, Chavin KD, Oates JC, Njoku C, Patrick KS, Fiorini RN, Markowitz JS. Oral administration of a decaffeinated green tea (Camellia sinensis) extract did not alter urinary 8-epi-prostaglandin F2a, a biomarker for in vivo lipid peroxidation. J Pharm Pharmacol 2005;57:1-5.