Pharmacokinetics, Pharmacodynamics and Drug Interactions

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

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 8069

Special Issue Editor

York College & Graduate Center, City University of New York, New York, NY, USA
Interests: pharmacokinetics; herb/food/drug-drug interaction; pharmacokinetics and pharmacodynamics modeling and simulation; drug-metabolizing enzymes and transporters; PBPK in special populations

Special Issue Information

Dear Colleagues,

Pharmacokinetics describes a drug’s absorption, distribution, metabolism and excretion and pharmacodynamics describes what a drug does to the body. Those are critical steps to understanding a drugs’ efficacy and safety. Several intrinsic and extrinsic factors could alter a drug’s pharmacokinetic and pharmacodynamics, including other drugs/food and natural products. Drug interactions may increase the action, cause the drug less effective, or have unexpected side effects.

This Special Issue will cover manuscripts that describe the results of basic, translational and clinical research that contribute significant and novel information on pharmacokinetics, pharmacodynamics and drug interactions. Areas include innovative mechanisms, approaches, and modeling and simulation. Original research articles, review articles, or commentaries are welcomed. 

Dr. Zhu Zhou
Guest Editor

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

  • pharmacokinetics
  • pharmacodynamics
  • drug metabolism
  • drug interaction
  • PK/PD modeling and simulation

Published Papers (5 papers)

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Research

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11 pages, 1574 KiB  
Article
Pharmacokinetic Interaction of Kratom and Cannabidiol in Male Rats
by Erin C. Berthold, Shyam H. Kamble, Siva Rama Raju Kanumuri, Michelle A. Kuntz, Alexandria S. Senetra, Yi-Hua Chiang, Sushobhan Mukhopadhyay, Christopher R. McCurdy and Abhisheak Sharma
Pharmaceutics 2024, 16(3), 318; https://doi.org/10.3390/pharmaceutics16030318 - 24 Feb 2024
Viewed by 2118
Abstract
Kratom and cannabidiol products are used to self-treat a variety of conditions, including anxiety and pain, and to elevate mood. Research into the individual pharmacokinetic properties of commercially available kratom and cannabidiol products has been performed, but there are no studies on coadministration [...] Read more.
Kratom and cannabidiol products are used to self-treat a variety of conditions, including anxiety and pain, and to elevate mood. Research into the individual pharmacokinetic properties of commercially available kratom and cannabidiol products has been performed, but there are no studies on coadministration of these products. Surveys of individuals with kratom use history indicate that cannabidiol use is one of the strongest predictors of both lifetime and past month kratom use. The purpose of this study was to determine if there are changes in pharmacokinetic properties when commercially available kratom and cannabidiol products are administered concomitantly. It was found that with concomitant administration of cannabidiol, there was a 2.8-fold increase in the exposure of the most abundant kratom alkaloid, mitragynine, and increases in the exposure of other minor alkaloids. The results of this work suggest that with cannabidiol coadministration, the effects of kratom may be both delayed and increased due to a delay in time to reach maximum plasma concentration and higher systemic exposure of the psychoactive alkaloids found in kratom. Full article
(This article belongs to the Special Issue Pharmacokinetics, Pharmacodynamics and Drug Interactions)
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17 pages, 1748 KiB  
Article
Sex and Cross-Sex Testosterone Treatment Alters Gamma-Hydroxybutyrate Acid Toxicokinetics and Toxicodynamics in Rats
by Qing Zhang, Hao Wei, Annie Lee and Melanie A. Felmlee
Pharmaceutics 2024, 16(1), 143; https://doi.org/10.3390/pharmaceutics16010143 - 21 Jan 2024
Viewed by 866
Abstract
Γ-hydroxybutyric acid (GHB) is widely abused due to its sedative/hypnotic and euphoric effects. In recent years, GHB use has witnessed a notable rise within the LGBTQ+ community. GHB is a substrate of monocarboxylate transporters (MCTs) and exhibits nonlinear toxicokinetics, characterized by saturable metabolism, [...] Read more.
Γ-hydroxybutyric acid (GHB) is widely abused due to its sedative/hypnotic and euphoric effects. In recent years, GHB use has witnessed a notable rise within the LGBTQ+ community. GHB is a substrate of monocarboxylate transporters (MCTs) and exhibits nonlinear toxicokinetics, characterized by saturable metabolism, absorption, and renal reabsorption. This study investigates the impact of exogenous testosterone administration on GHB toxicokinetics and toxicodynamics, exploring the potential of MCT1 inhibition as a strategy to counteract toxicity. Ovariectomized (OVX) females and castrated (CST) male Sprague Dawley rats were treated with testosterone or placebo for 21 days. GHB was administered at two doses (1000 mg/kg or 1500 mg/kg i.v.), and the MCT1 inhibitor AR-C 155858 (1 mg/kg i.v.) was administered 5 min after GHB (1500 mg/kg i.v.) administration. Plasma and urine were collected up to 8 h post-dose, and GHB concentrations were quantified via a validated LC/MS/MS assay. Sleep time (sedative/hypnotic effect) was utilized as the toxicodynamic endpoint. Testosterone treatment significantly affected GHB toxicokinetics and toxicodynamics. Testosterone-treated CST rats exhibited significantly lower renal clearance, higher AUC, and increased sedative effect, while testosterone-treated OVX rats demonstrated higher metabolic clearance. AR-C 155858 treatment led to an increase in GHB renal and total clearance together with an improvement in sedative/hypnotic effect. In conclusion, exogenous testosterone treatment induces significant alterations in GHB toxicokinetics and toxicodynamics, and MCT inhibition can serve as a potential therapeutic strategy for GHB overdose in both cisgender and transgender male populations. Full article
(This article belongs to the Special Issue Pharmacokinetics, Pharmacodynamics and Drug Interactions)
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23 pages, 4466 KiB  
Article
Population Pharmacokinetic Modeling for Twice-Daily Intravenous Busulfan in a Large Cohort of Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation—A 10-Year Single-Center Experience
by Katharina M. Schreib, Dominic S. Bräm, Ulrike Barbara Zeilhofer, Daniel Müller, Tayfun Güngör, Stefanie D. Krämer and Mathias M. Hauri-Hohl
Pharmaceutics 2024, 16(1), 13; https://doi.org/10.3390/pharmaceutics16010013 - 20 Dec 2023
Viewed by 798
Abstract
Reaching target exposure of busulfan-based conditioning prior to hematopoietic stem cell transplantation is vital for favorable therapy outcomes. Yet, a wide inter-patient and inter-occasion variability in busulfan exposure has been reported, especially in children. We aimed to identify factors associated with the variability [...] Read more.
Reaching target exposure of busulfan-based conditioning prior to hematopoietic stem cell transplantation is vital for favorable therapy outcomes. Yet, a wide inter-patient and inter-occasion variability in busulfan exposure has been reported, especially in children. We aimed to identify factors associated with the variability of busulfan pharmacokinetics in 124 consecutive patients transplanted at the University Children’s Hospital Zurich between October 2010 and February 2020. Clinical data and busulfan plasma levels after twice-daily intravenous administration were analyzed retrospectively by population pharmacokinetic modeling. The volume of distribution correlated with total body water. The elimination rate constant followed an age-dependent maturation function, as previously suggested, and correlated with the levels of serum albumin. Acute lymphoblastic leukemia reduced busulfan clearance by 20%. Clearance significantly decreased by 17% on average from the start to the third day of busulfan administration, in agreement with other studies. An average reduction of 31% was found in patients with hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease. In conclusion, we demonstrate that in addition to known factors, underlying disease and serum albumin significantly impact busulfan pharmacokinetics in pediatric patients; yet, substantial unexplained variability in some patients remained. Thus, we consider repeated pharmacokinetic assessment essential to achieve the desired target exposure in twice-daily busulfan administration. Full article
(This article belongs to the Special Issue Pharmacokinetics, Pharmacodynamics and Drug Interactions)
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10 pages, 1701 KiB  
Article
Pharmacodynamic and Pharmacokinetic Drug Interactions between Fexuprazan, a Novel Potassium-Competitive Inhibitor, and Aspirin, in Healthy Subjects
by JungJin Oh, Eunsol Yang, In-Jin Jang, Hyejung Lee, Hokyun Yoo, Jae-Yong Chung, SeungHwan Lee and Jaeseong Oh
Pharmaceutics 2023, 15(2), 549; https://doi.org/10.3390/pharmaceutics15020549 - 07 Feb 2023
Cited by 1 | Viewed by 2800
Abstract
Acid-reducing agents are commonly used for the prevention of aspirin-induced gastrointestinal complications such as peptic ulcers. As a novel potassium-competitive acid blocker, fexuprazan is expected to prevent aspirin-induced gastrointestinal complications. This randomized, open-label study aimed to evaluate the pharmacodynamic and pharmacokinetic interactions between [...] Read more.
Acid-reducing agents are commonly used for the prevention of aspirin-induced gastrointestinal complications such as peptic ulcers. As a novel potassium-competitive acid blocker, fexuprazan is expected to prevent aspirin-induced gastrointestinal complications. This randomized, open-label study aimed to evaluate the pharmacodynamic and pharmacokinetic interactions between aspirin and fexuprazan in healthy Koreans. Subjects randomized to the aspirin group received 500 mg aspirin in combination with 80 mg fexuprazan. For the fexuprazan group, fexuprazan 80 mg was administered alone and then in combination with aspirin 500 mg. Platelet aggregation inhibited by aspirin and the pharmacokinetic parameters of aspirin and fexuprazan were compared between monotherapy and combination therapy. A total of 22 subjects completed the study. The platelet aggregation-inhibitory activity and systemic exposure to aspirin were not significantly affected by fexuprazan coadministration. The systemic exposure of fexuprazan was decreased up to 20% by aspirin coadministration, which was not regarded as clinically meaningful considering the previously reported exposure–response relationship. In conclusion, there were no clinically relevant pharmacodynamic or pharmacokinetic interactions between aspirin and fexuprazan. This finding suggests the potential of fexuprazan for the prevention of aspirin-induced gastrointestinal complications, serving as a baseline for optimizing its therapeutic application with aspirin. Full article
(This article belongs to the Special Issue Pharmacokinetics, Pharmacodynamics and Drug Interactions)
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Review

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27 pages, 483 KiB  
Review
CBD and THC in Special Populations: Pharmacokinetics and Drug–Drug Interactions
by Lixuan Qian, Jessica L. Beers, Klarissa D. Jackson and Zhu Zhou
Pharmaceutics 2024, 16(4), 484; https://doi.org/10.3390/pharmaceutics16040484 - 01 Apr 2024
Viewed by 580
Abstract
Cannabinoid use has surged in the past decade, with a growing interest in expanding cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) applications into special populations. Consequently, the increased use of CBD and THC raises the risk of drug–drug interactions (DDIs). Nevertheless, DDIs for cannabinoids, especially [...] Read more.
Cannabinoid use has surged in the past decade, with a growing interest in expanding cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) applications into special populations. Consequently, the increased use of CBD and THC raises the risk of drug–drug interactions (DDIs). Nevertheless, DDIs for cannabinoids, especially in special populations, remain inadequately investigated. While some clinical trials have explored DDIs between therapeutic drugs like antiepileptic drugs and CBD/THC, more potential interactions remain to be examined. This review summarizes the published studies on CBD and THC–drug interactions, outlines the mechanisms involved, discusses the physiological considerations in pharmacokinetics (PK) and DDI studies in special populations (including pregnant and lactating women, pediatrics, older adults, patients with hepatic or renal impairments, and others), and presents modeling approaches that can describe the DDIs associated with CBD and THC in special populations. The PK of CBD and THC in special populations remain poorly characterized, with limited studies investigating DDIs involving CBD/THC in these populations. Therefore, it is critical to evaluate potential DDIs between CBD/THC and medications that are commonly used in special populations. Modeling approaches can aid in understanding these interactions. Full article
(This article belongs to the Special Issue Pharmacokinetics, Pharmacodynamics and Drug Interactions)
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