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Pharmaceutics
Special Issues
Pharmacokinetics and Drug–Drug Interactions of Novel Psychotropic Drugs
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Pharmacokinetics and Drug–Drug Interactions of Novel Psychotropic Drugs

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 2656

Special Issue Editors

Dr. Przemysław J. Danek

E-Mail Website
Guest Editor
Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland
Interests: psychopharmacology; antidepressants; antipsychotics; drug development; drug metabolism; drug–drug interactions; cytochrome P450
Dr. Anna Haduch

E-Mail Website
Guest Editor
Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Poland
Interests: psychopharmacology; brain metabolism; cytochrome P450; drug metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Psychotropic drugs (antipsychotics, antidepressants, mood stabilizers, anxiolytics) have been playing an increasing role in the treatment of mental disorders for over half a century. They have offered substantial relief from some debilitating symptoms like auditory hallucinations, depression, and excessive mood fluctuations. Psychotropics are used as monotherapy, as well as adjunctive or augmentation therapy in several psychiatric disorders. Pharmacotherapy with psychotropic drugs is carried out for months/years, very often in combination with drugs from other pharmacological groups. Concomitant therapy with psychotropics may result in pharmacokinetic interactions that produce adverse reactions. The majority of clinically relevant pharmacokinetic drug–drug interactions with psychotropics occur as a consequence of drug-induced changes in hepatic metabolism. The most frequently reported cases of drug–drug interactions include the modulation of psychotropic drugs on drug-metabolizing enzymes and transporters and the causative pharmacokinetic effect of co-administered therapeutic drugs that are substrates for drug-metabolizing enzymes and transporters.

Therefore, this Special Issue aims to highlight the pharmacokinetics and drug interactions of novel psychotropic drugs and their mechanistic understanding concerning drug-metabolizing enzymes and drug transporters.

In this Special Issue of Pharmaceutics, we invite you to contribute original research articles or reviews on all aspects of the theme “Pharmacokinetics and Drug–Drug Interactions of Novel Psychotropic Drugs”. Expert articles describing new aspects of pharmacokinetics, ADME, drug–drug interactions, or new aspects of novel psychotropic drug actions are highly welcome.

Dr. Przemysław J. Danek
Dr. Anna Haduch
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • psychiatric disorders
  • new drugs
  • psychotropic drugs
  • antidepressants
  • antipsychotics
  • drug development
  • therapy
  • targets

Published Papers (2 papers)

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Research

14 pages, 1303 KiB  
Article
Cannabinoid-Induced Inhibition of Morphine Glucuronidation and the Potential for In Vivo Drug–Drug Interactions
by Shelby Coates, Keti Bardhi and Philip Lazarus
Pharmaceutics 2024, 16(3), 418; https://doi.org/10.3390/pharmaceutics16030418 - 18 Mar 2024
Viewed by 1343
Abstract
Opioids are commonly prescribed for the treatment of chronic pain. Approximately 50% of adults who are prescribed opioids for pain co-use cannabis with their opioid treatment. Morphine is primarily metabolized by UDP-glucuronosyltransferase (UGT) 2B7 to an inactive metabolite, morphine-3-glucuronide (M3G), and an active [...] Read more.
Opioids are commonly prescribed for the treatment of chronic pain. Approximately 50% of adults who are prescribed opioids for pain co-use cannabis with their opioid treatment. Morphine is primarily metabolized by UDP-glucuronosyltransferase (UGT) 2B7 to an inactive metabolite, morphine-3-glucuronide (M3G), and an active metabolite, morphine-6-glucuronide (M6G). Previous studies have shown that major cannabis constituents including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) inhibit major UGT enzymes. To examine whether cannabinoids or their major metabolites inhibit morphine glucuronidation by UGT2B7, in vitro assays and mechanistic static modeling were performed with these cannabinoids and their major metabolites including 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (11-COOH-THC), 7-hydroxy-cannabidiol (7-OH-CBD), and 7-carboxy-cannabidiol (7-COOH-CBD). In vitro assays with rUGT-overexpressing microsomes and human liver microsomes showed that THC and CBD and their metabolites inhibited UGT2B7-mediated morphine metabolism, with CBD and THC exhibiting the most potent Ki,u values (0.16 µM and 0.37 µM, respectively). Only 7-COOH-CBD exhibited no inhibitory activity against UGT2B7-mediated morphine metabolism. Static mechanistic modeling predicted an in vivo drug–drug interaction between morphine and THC after inhaled cannabis, and between THC, CBD, and 7-OH-CBD after oral consumption of cannabis. These data suggest that the co-use of these agents may lead to adverse drug events in humans. Full article
(This article belongs to the Special Issue Pharmacokinetics and Drug–Drug Interactions of Novel Psychotropic Drugs)
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17 pages, 1881 KiB  
Article
Cannabinoid-Induced Stereoselective Inhibition of R-S-Oxazepam Glucuronidation: Cannabinoid–Oxazepam Drug Interactions
by Keti Bardhi, Shelby Coates, Gang Chen and Philip Lazarus
Pharmaceutics 2024, 16(2), 243; https://doi.org/10.3390/pharmaceutics16020243 - 07 Feb 2024
Viewed by 883
Abstract
Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and are frequently used in conjunction with other illicit drugs including cannabis. Oxazepam is metabolized in an enantiomeric-specific manner by glucuronidation, with S-oxazepam [...] Read more.
Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and are frequently used in conjunction with other illicit drugs including cannabis. Oxazepam is metabolized in an enantiomeric-specific manner by glucuronidation, with S-oxazepam metabolized primarily by UGT2B15 and R-oxazepam glucuronidation mediated by both UGT 1A9 and 2B7. The goal of the present study was to evaluate the potential inhibitory effects of major cannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), and major THC metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (11-COOH-THC), on the UGT-mediated metabolism of R- and S-oxazepam. The cannabinoids and metabolites were screened as inhibitors of R- and S-oxazepam glucuronidation in microsomes isolated from HEK293 cells overexpressing individual UGT enzymes (rUGTs). The IC50 values were determined in human liver microsomes (HLM), human kidney microsomes (HKM), and rUGTs and utilized to estimate the nonspecific, binding-corrected Ki (Ki,u) values and predict the area under the concentration–time curve ratio (AUCR). The estimated Ki,u values observed in HLM for S- and R-oxazepam glucuronidation by CBD, 11-OH-THC, and THC were in the micromolar range (0.82 to 3.7 µM), with the Ki,u values observed for R-oxazepam glucuronidation approximately 2- to 5-fold lower as compared to those observed for S-oxazepam glucuronidation. The mechanistic static modeling predicted a potential clinically significant interaction between oral THC and CBD with oxazepam, with the AUCR values ranging from 1.25 to 3.45. These data suggest a pharmacokinetic drug–drug interaction when major cannabinoids like CBD or THC and oxazepam are concurrently administered. Full article
(This article belongs to the Special Issue Pharmacokinetics and Drug–Drug Interactions of Novel Psychotropic Drugs)
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