About

John S Markowitz, Pharm.D., BCPP, is a professor in the Department of Pharmacotherapy & Translational Research at the University of Florida College of Pharmacy. He received his BS in Biology from Memphis State University and his Doctorate in Pharmacy from the University of Tennessee Center for the Health Sciences. He completed an ASHP-accredited specialty residency in Psychiatric Pharmacy Practice at UTCHS. Dr. Markowitz served for a decade as a Clinical Specialist in Psychiatry and as Clinical Coordinator within the Institute of Psychiatry at the Medical University of South Carolina, where he also held a faculty research position in the Department of Pharmaceutical & Biomedical Sciences with a dual appointment in the Department of Psychiatry and Behavioral Sciences. He has been credentialed by the Board of Pharmaceutical Specialties in Psychiatric Pharmacy since 1997 and is a founding member of the College of Psychiatric and Neurologic Pharmacists. His research encompasses in vitro and in vivo investigations into drug-drug interactions, botanical-drug interactions, and their clinical effects, with recent focus on variability in drug metabolism, disposition, and therapeutic response influenced by genetic variability, particularly involving the serine esterase carboxylesterase 1 (CES1). Dr. Markowitz has received research support from industry and NIH institutes, serving as principal investigator on multiple grants. His work has resulted in numerous peer-reviewed publications, and his laboratory focuses on individual variability in drug response, especially related to neuropsychiatric medications, through studies on drug metabolism, pharmacogenomics, and transporter interactions.

Research topics

• Medicine
• Internal medicine
• Biology
• Pharmacology
• Veterinary medicine
• Chemistry
• Traditional medicine
• Anesthesia
• Biochemistry

Selected publications

• Formulation-dependent dissolution and bioaccessibility of curcuminoids and (S)-ar-turmerone from eight commercial turmeric extract- and curcumin-containing dietary supplements

  Pharmaceutical Biology · 2026-02-23 · 1 citations

  articleOpen accessSenior author

  CONTEXT: Curcumin-containing dietary supplements are widely marketed with claims of enhanced bioavailability, despite well-recognized limitations related to poor aqueous solubility, chemical instability, and extensive first-pass metabolism. Comparisons among commercially available products using physiologically relevant performance metrics remain limited. OBJECTIVE: To systematically evaluate disintegration, dissolution, and bioaccessibility of curcuminoids and (S)-ar-turmerone from a cross section of commercially available turmeric dietary supplements under fasted- and fed-state biorelevant conditions. MATERIALS AND METHODS: Eight marketed turmeric supplements representing diverse formulation strategies were assessed for disintegration and dissolution using USP-aligned methods in fasted- and fed-state simulated gastric and intestinal media (FaSSGF, FaSSIF, FeSSGF, FeSSIF). Bioaccessible concentrations, quantities, and dose fractions of curcuminoids and (S)-ar-turmerone were quantified after 3 h. RESULTS: All products exhibited poor dissolution overall, with no formulation achieving greater than 40% total release. Dissolution was lowest under fasted-state conditions and improved modestly in fed-state gastric media, reflecting the influence of lipid content. Products with higher curcuminoid loads per capsule generated greater absolute bioaccessible concentrations despite poor release efficiency, whereas a phytosome formulation achieved superior release despite a lower dose. Several products marketed as "enhanced" formulations demonstrated poor disintegration and low bioaccessibility. DISCUSSION: These findings indicate that bioaccessible concentration is governed jointly by dosage-form performance and curcuminoid dose loading, and that plasma exposure metrics dominated by conjugated metabolites may not reliably reflect formulation performance. CONCLUSION: release is a prerequisite - but not a guarantee - for enhanced systemic exposure, underscoring the need for cautious interpretation of bioavailability claims.

  PublisherDOI

• Steroid Hormone Changes After Short-term High-Dose Exposure to Cannabidiol in Healthy Subjects: An Exploratory Study

  Medical Cannabis and Cannabinoids · 2026-04-21

  articleOpen accessSenior author

  Introduction: Cannabis-derived cannabidiol (CBD; Epidiolex®) is FDA-approved for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex, yet its effects on human steroid hormone regulation remain unclear. This study evaluated changes in five plasma steroid hormones and one precursor bile acid after short-term high-dose oral CBD administration in healthy subjects. Methods: Twelve participants (6 males, 6 females) completed a randomized, placebo-controlled crossover study and received oral CBD 750 mg twice daily for 3.5 days or placebo, separated by a washout period. All subjects received methylphenidate on the final clinical day for an additional independent study objective. Plasma samples collected after the final dose were analyzed by LC–MS/MS. Statistical analyses assessed CBD-associated hormonal changes and correlations with CBD and metabolite concentrations. This study was supported in part by the State of Florida Consortium for Medical Marijuana Clinical Outcomes Research. Results: A significant decrease in the precursor steroid 21-OH-progesterone was observed in the CBD group compared with the placebo group. Cortisol and corticosterone levels increased consistently across all CBD-administered participants, and testosterone levels rose significantly in male subjects. No significant differences were identified between the CBD and placebo groups in cholic acid concentrations. All measured hormone levels remained within physiological ranges, and their clinical significance is uncertain. Conclusion: Overall, this study provides novel, though preliminary evidence that CBD may modulate key components of the steroidogenic and endocrine systems in humans.

  PublisherOA PDFDOI

• An in vitro evaluation of common botanical extracts on carboxylesterase 1 catalytic activity

  Drug Metabolism and Disposition · 2025-07-21

  articleSenior author
  PublisherDOI

• Increased plasma concentrations of 6-oxo-methylphenidate in CES1 G134E carriers following a single oral dose of methylphenidate

  Medicinal Chemistry Research · 2025-10-02

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Charleston Antidepressant Drug Interactions Surveillance Program (CADISP)

  Psychopharmacology Bulletin · 2025-08-12

  article

  A prospective antidepressant drug interaction surveillance program was established and collected data for over 4 years in Charleston, SC (Charleston Antidepressant Drug Interactions Surveillance Program, CADISP). One hundred and seventy patients were enrolled. The plasma concentrations and/or clinical effects of drug combinations were monitored in psychiatric patients who received therapy with a selective serotonin reuptake inhibitor (SSRI) or one of the other newer antidepressants (nefazodone, venlafaxine) when combined with other drugs metabolized by the cytochrome P-450 (CYP) enzyme system. Patient data were evaluated to estimate the occurrence and significance of antidepressant-induced metabolic drug interactions. Plasma drug concentrations in the presence and absence of treatment with an antidepressant served as the primary assessment variable. Contrary to the hypothesis that pharmacokinetic drug–drug interactions occur but go undetected, little evidence was found for occultly occurring drug interactions with newer antidepressants. The presence of commonly predicted drug interactions was documented. These data do not eliminate the need for caution when prescribing antidepressants with the potential for causing metabolic interactions, but do help allay the fear that such interactions are highly prevalent and routinely hazardous.

  PublisherDOI

• A Pharmacokinetic Drug-Drug Interaction Study of Venlafaxine and Indinavir

  Psychopharmacology Bulletin · 2025-08-12 · 39 citations

  article

  Depression is a common occurrence in the human immunodeficiency virus (HIV)-infected population. Complications in treating depressed HIV-infected individuals include the use of multiple medications, additive side effects, and potentially significant drug-drug interactions. Based on the pharmacologic characteristics of venlafaxine and indinavir, we hypothesized that significant pharmacokinetic drug-drug interactions would not occur when these drugs where taken concurrently. Nine healthy adult subjects were given a single 800 mg oral dose of indinavir and serial blood samples were collected for measurement of plasma drug concentrations. Over the next 9 days, venlafaxine was administered at a dosage of 50 mg every 8 hours following a brief titration. A venlafaxine trough plasma concentration and serial concentrations following venlafaxine administration were obtained on day 10. On day 11, venlafaxine and indinavir were administered together and serial blood sampling was repeated. Indinavir had no effect on venlafaxine plasma concentrations but resulted in a 7% decrease in plasma concentrations of O-desmethyl-venlafaxine (ODV)(P = 0.028). This effect is unlikely to be clinically significant. Venlafaxine coadministration resulted in a 28% decrease in the area under the concentration time curve (AUC) of plasma indinavir (P = 0.016) and a 36% decrease in its maximum plasma concentration (Cmax; P = 0.038). As the plasma concentration of protease inhibitors is a critical factor in maintaining efficacy and minimizing the potential for viral resistance, the decrease in both AUC and Cmax of indinavir from coadministration of venlafaxine is of concern. The clinical significance of these results obtained from a small number of healthy volunteers is unknown. Further studies are needed to substantiate or refute this apparent drug-drug interaction. Until such time, venlafaxine should be used cautiously in patients receiving indinavir.

  PublisherDOI

• Central nervous system stimulants in recreational and medical use

  CNS Spectrums · 2025-01-01 · 5 citations

  reviewOpen accessSenior author

  Stimulants that act on the central nervous system have been used since antiquity for ritual and other uses. Organic chemistry techniques, especially those developed in Germany in the late 1800s, resulted in the isolation and structural determination of several important stimulants. Synthetic pathways for amphetamine and related stimulants were developed in the first half of the 19th century, and these new drugs were widely marketed. Awareness of abuse potential emerged soon after but was contested. Stimulants have been used to counteract fatigue and promote wakefulness during military operations, as well as to treat sleep disorders, since the 1930s. Methylphenidate was approved to treat children with behavioral problems in 1962, predating the recognition of attention deficit hyperactivity disorder (ADHD). Stimulant abuse became a political concern in the post-war period, initially with the use of "pep-pills" by long-haul truck drivers and later as drug dealing became common in night clubs, with new laws limiting availability passed in the early 1960s. They have also been used to increase athletic and cognitive performance. Stimulants are still first-line therapies for ADHD and some sleep disorders; however, newer-generation drugs have been developed with better safety profiles and lower abuse potential. Illicit stimulant use continues to be common in many countries.

  PublisherOA PDFDOI

• Evaluating reversible inhibitory drug–drug interactions: enzyme kinetics, and <i>in vitro</i>-to-<i>in vivo</i> scaling models

  Journal of Pharmacy and Pharmacology · 2025-06-20 · 3 citations

  articleSenior author

  BACKGROUND: Polypharmacy is common in clinical practice, making the consideration of potential drug-drug interactions (DDIs) an important factor in clinical therapeutics. In vitro methods are applied for screening and anticipating possible DDIs, with mathematical models playing a key role in evaluating inhibitor potency and scaling pharmacokinetic parameters from in vitro data. Despite extensive research on this topic, varying assumptions and experimental settings across studies have led to inconsistency among models, with the possible consequence of misapplication of enzyme kinetic models and scaling procedures, and misdirection in DDI evaluation and predictions. METHODS: This study reviews and summarizes common enzyme kinetic models used to analyse substrate-enzyme-inhibitor interactions across six different mechanisms of inhibition, and derives the corresponding in vitro to in vivo scaling model for use in connecting to clinical DDI studies. RESULTS: A single operational equation was developed, along with a method for determining the inhibition mechanism and the connection to anticipation of in vivo pharmacokinetics. CONCLUSION: Analysis based on the equation shows that, for inhibitors with the same inhibition constant (Ki), competitive inhibitors will pose a higher potential for DDIs compared to non-competitive inhibitors, while complete inhibitors will result in a higher potential for DDI than partial inhibitors.

  PublisherDOI

• Ketoconazole Inhibition of Gepirone Biotransformation and Clearance: In Vitro and Clinical Studies

  The Journal of Clinical Pharmacology · 2025-06-19 · 1 citations

  article

  Abstract Gepirone, an antidepressant drug, is biotransformed into two principal metabolites [1‐(2‐pyrimidinyl)‐piperazine (1‐PP) and 3′‐OH‐gepirone] primarily by CYP3A enzymes. Metabolism of gepirone in the presence of ketoconazole, a potent inhibitor of human CYP3A activity, was studied in vitro in human liver microsomes. The clinical pharmacokinetic interaction of ketoconazole (as a maximal chemical inhibitor of CYP3A isoforms) with single doses of gepirone was evaluated in a Phase 1 study in human volunteers (N = 24). In vitro coincubation of gepirone with increasing concentrations of ketoconazole produced extensive inhibition of 1‐PP and 3′‐OH‐gepirone formation, with IC 50 values in the range of 0.026 µM to 0.162 µM. These inhibitory values are substantially lower than clinically encountered systemic concentrations of ketoconazole, thereby predicting extensive in vivo increases in gepirone exposure when coadministered with ketoconazole. In the clinical pharmacokinetic study, ketoconazole produced large increases in gepirone exposure by factors of 5.92‐ to 7.80‐fold. Appearance of 1‐PP in the systemic circulation decreased by factors of 0.56 to 0.97, while appearance of 3′‐OH‐gepirone increased by 1.70‐ to 2.43‐fold. The clinical findings are consistent with the in vitro results, and underlie the labeling recommendation that gepirone not be coadministered with “strong” CYP3A inhibitors.

  PublisherDOI

• The Emerging Recognition of Herb-Drug Interactions With a Focus on St. John’s Wort (Hypericum Perforatum)

  Psychopharmacology Bulletin · 2025-08-12 · 45 citations

  article1st authorCorresponding

  The use of herbal medications and other alternative therapies is accelerating. Survey data clearly indicate that these agents are frequently combined with prescription and over-the-counter medications. The herbal antidepressant St. John's wort (Hypericum perforatum) is one of the most commonly utilized herbal agents. In spite of growing concern and examples of herb-drug interactions, little systematic research has been published or funded in this area. Computerized searches of the biomedical literature were undertaken utilizing MEDLINE, Current Contents, and PsycINFO computer databases (years 1966-December 2000) and by review of bibliographies to identify all pertinent case reports, case series, and formal studies for this review using search terms St. John's wort, hypericum, herb, in vitro, cytochrome P450, and drug interactions. Little in vitro or in vivo data on St John's wort or other herb-drug interactions is available and current in vitro methods for screening conventional medications may have limited applications to herbal agents which generally have numerous constituents of unknown pharmacokinetics and pharmacology. However, available data from clinical studies and case reports suggests that St. John's wort is unlikely to inhibit cytochrome P450 (CYP) 3A4 or 2D6, but is likely an inducer of CYP 3A4 and possibly the P-glycoprotein transporter. Examples of conventional medications which may undergo significant CYP 3A4 induction by St. John's wort include cyclosporine, indinavir, and oral contraceptives. The accumulating evidence of significant drug interactions with St. John's wort should serve as an example to clinicians to be aware of the potential for St. John's wort, and very likely, other herbal products to participate in important herb-drug interactions when used in combination with conventional medications. Concomitant use of herbal agents and conventional medications should generally be discouraged until further information is available. Additional research is urgently needed in this area.

  PublisherDOI

Recent grants

• NIH Grant M01RR001070

  NIH · $3.9M · 2010

• NIH Grant R21AT002817

  NIH · $576k · 2009

• NIH Grant R21AI096345

  NIH · $403k · 2014

• NIH Grant R21HD047810

  NIH · $402k · 2007

• NIH Grant R01DA022475

  NIH · $1.3M · 2012

Frequent coauthors

• Hao‐Jie Zhu

  Jiangxi Agricultural University

  86 shared

• C. Lindsay DeVane

  Medical University of South Carolina

  55 shared

• Kennerly S. Patrick

  55 shared

• Jennifer L. Donovan

  36 shared

• Hilary J. Bernstein

  University of California, Santa Barbara

  34 shared

• Kenneth D. Chavin

  Case Western Reserve University

  33 shared

• Bryan J. Brinda

  30 shared

• Arthur B. Straughn

  University of Tennessee Health Science Center

  21 shared

Education

• Ph.D., Pharmaceutical & Biomedical Sciences

  Medical University of South Carolina (MUSC)

Awards & honors

• Outstanding Teaching Team- Year 3 Award, Patient Care VII, T…
• Outstanding Teaching Team- Year 3 Award, Patient Care VII, T…
• MUSC College of Pharmacy Professor of the Year 2005-2006