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Advances in Pharmacokinetic Drug–Drug Interactions

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 2393

Special Issue Editors


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Guest Editor
Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Magee-Womens Research Institute, 204 Craft Avenue, Pittsburgh, PA 15213, USA
Interests: in vitro ADME; in vivo DMPK; drug-drug interactions; PBPK modeling; drug discovery and development
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Guest Editor
Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India
Interests: diabetes; PK-PD; metabolic syndrome; in vitro ADME; in vivo DMPK; drug discovery and development

Special Issue Information

Dear Colleagues,

The investigation of drug–drug interactions is essential for drug discovery and development. The important mechanisms for pharmacokinetic drug–drug interactions include the inhibition or induction of drug metabolism and transporters. It is essential to evaluate absorption, distribution, metabolism, excretion (ADME) and pharmacokinetic interactions of novel molecules, and investigational drugs for effective drug development. Remarkable progress has been made over the past few decades in ADME and DMPK tools that can promote the development of novel therapies and advances in understanding the effects of diseases on PK and minimize the potential of drug–drug interactions and reduce attrition rates in drug development. This Special Issue welcomes the submission of original research and/or review articles on drug discovery and development related to the advancements of in vitro, in vivo, and ex vivo ADME and DMPK, in vitro to in vivo correlation and extrapolation (IVIVC/E), biotransformation, drug–drug interactions, and pharmacokinetic interactions related to drug-metabolizing enzymes and drug transporters. This Special Issue will promote a quantitative and mechanistic understanding of the pharmacokinetic interactions of novel drug candidates in biological systems. 

Dr. Guru Raghavendra Valicherla
Dr. Jiaur Rahaman Gayen
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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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

  • liquid chromatography mass spectrometry
  • in vitro adme (absorption, distribution, metabolism, excretion)
  • in vivo pharmacokinetics and drug metabolism
  • drug–drug interactions
  • drug metabolizing enzymes
  • drug transporters

Published Papers (1 paper)

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Research

18 pages, 2035 KiB  
Article
Simultaneous Estimation of Quercetin and trans-Resveratrol in Cissus quadrangularis Extract in Rat Serum Using Validated LC-MS/MS Method: Application to Pharmacokinetic and Stability Studies
by Shailesh D. Dadge, Anees A. Syed, Athar Husain, Guru R. Valicherla and Jiaur R. Gayen
Molecules 2023, 28(12), 4656; https://doi.org/10.3390/molecules28124656 - 8 Jun 2023
Viewed by 2148
Abstract
Cissus quadrangularis is a nutrient-rich plant with a history of use in traditional medicine. It boasts a diverse range of polyphenols, including quercetin, resveratrol, β-sitosterol, myricetin, and other compounds. We developed and validated a sensitive LC-MS/MS method to quantify quercetin and t-res [...] Read more.
Cissus quadrangularis is a nutrient-rich plant with a history of use in traditional medicine. It boasts a diverse range of polyphenols, including quercetin, resveratrol, β-sitosterol, myricetin, and other compounds. We developed and validated a sensitive LC-MS/MS method to quantify quercetin and t-res biomarkers in rat serum and applied this method to pharmacokinetic and stability studies. The mass spectrometer was set to negative ionization mode for the quantification of quercetin and t-res. Phenomenex Luna (C18(2), 100 A, 75 × 4.6 mm, 3 µ) column was utilized to separate the analytes using an isocratic mobile phase consisting of methanol and 0.1% formic acid in water (82:18). Validation of the method was performed using various parameters, including linearity, specificity, accuracy, stability, intra-day, inter-day precision, and the matrix effect. There was no observed significant endogenous interference from the blank serum. The analysis was completed within 5.0 min for each run, and the lower limit of quantification was 5 ng/mL. The calibration curves showed a linear range with a high correlation coefficient (r2 > 0.99). The precision for intra- and inter-day assays showed relative standard deviations from 3.32% to 8.86% and 4.35% to 9.61%, respectively. The analytes in rat serum were stable during bench-top, freeze-thaw, and autosampler (−4 °C) stability studies. After oral administration, the analytes showed rapid absorption but underwent metabolism in rat liver microsomes despite being stable in simulated gastric and intestinal fluids. Intragastric administration resulted in higher absorption of quercetin and t-res, with greater Cmax, shorter half-life, and improved elimination. No prior research has been conducted on the oral pharmacokinetics and stability of anti-diabetic compounds in the Ethanolic extract of Cissus quadrangularis EECQ, making this the first report. Our findings can provide the knowledge of EECQ’s bioanalysis and pharmacokinetic properties which is useful for future clinical trials. Full article
(This article belongs to the Special Issue Advances in Pharmacokinetic Drug–Drug Interactions)
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