Several commonly used opioid analgesics, such as fentanyl, sufentanil, alfentanil, and hydrocodone, are by report primarily metabolized by the CYP3A4 enzyme. The concurrent use of ritonavir, a potent CYP3A4 inhibitor, can lead to significant drug interactions. Using physiologically based pharmacokinetic (PBPK) modeling and simulation, this study examines the effects of different dosing regimens of ritonavir on the pharmacokinetics of these opioids. The findings reveal that co-administration of ritonavir significantly increases the exposure of fentanyl analogs, with over a 10-fold increase in the exposure of alfentanil and sufentanil when given with ritonavir. Conversely, the effect of ritonavir on fentanyl exposure is modest, likely due to additional metabolism pathways. Additionally, the study demonstrates that the steady-state exposure of hydrocodone and its active metabolite hydromorphone can be increased by up to 87% and 95%, respectively, with concurrent use of ritonavir. The extended-release formulation of hydrocodone is particularly affected. These insights from PBPK modeling provide valuable guidance for optimizing opioid dosing and minimizing the risk of toxicity when used in combination with ritonavir-containing prescriptions.
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http://dx.doi.org/10.3390/ph17050640 | DOI Listing |
PLoS One
January 2025
Centre for Regenerative Medicine and Devices, University of Brighton, Brighton, United Kingdom.
Diabetic foot, leg ulcers and decubitus ulcers affect millions of individuals worldwide leading to poor quality of life, pain and in several cases to limb amputations. Despite the global dimension of this clinical problem, limited progress has been made in developing more efficacious wound dressings, the design of which currently focusses on wound protection and control of its exudate volume. The present in vitro study systematically analysed seven types of clinically-available wound dressings made of different biomaterial composition and engineering.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Computer Science and Engineering, University of Chittagong, Chattogram, Bangladesh.
Rice blast, caused by Magnaporthe oryzae, is one of the most destructive fungal diseases in rice, resulting in major economic losses worldwide. Genetic and genomic studies have identified key genes and proteins, such as AvrPik variants and MAX proteins, that are crucial for the pathogen's virulence. These effector proteins interact with specific alleles of the Pik gene family on rice chromosome 11, modulating the host's immune response.
View Article and Find Full Text PDFCrit Rev Anal Chem
January 2025
Department of Bioengineering, Faculty of Engineering, The University of Edinburgh, Edinburgh, UK.
Cells are the fundamental units of life, comprising a highly concentrated and complex assembly of biomolecules that interact dynamic ally across spatial and temporal scales. Living cells are constantly undergoing dynamic processes, therefore, to understand the interactions between drug molecules and living cells is of paramount importance in the biomedical sciences and pharmaceutical development. Compared with traditional end-point assays and fixed cell analysis, analysis of drug molecules in living cells can provide more insight into the effects of drugs on cells in real-time and allowing for a better understanding of drug mechanisms and effects, which will contribute to the development of drug developing and testing and personalize medicine.
View Article and Find Full Text PDFAnnu Rev Pathol
January 2025
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA; email:
Over the last two decades, there have been extensive efforts to develop small-molecule inhibitors of protein-protein interactions (PPIs) as novel therapeutics for cancer, including hematologic malignancies. Despite the numerous challenges associated with developing PPI inhibitors, a significant number of them have advanced to clinical studies in hematologic patients in recent years. The US Food and Drug Administration approval of the very first PPI inhibitor, venetoclax, demonstrated the real clinical value of blocking protein-protein interfaces.
View Article and Find Full Text PDFClin Orthop Relat Res
January 2025
Department of Medicine, Duke University, Durham, NC, USA.
Background: Rifampin therapy is indicated for the treatment of staphylococcal periprosthetic joint infection (PJI) in patients who have undergone debridement, antibiotics, and implant retention (DAIR) or one-stage revision as per the Infectious Diseases Society of America (IDSA) guideline. Given the well-established effectiveness of rifampin as adjunctive therapy in staphylococcal PJI, it is crucial to evaluate its utilization in practice and identify factors that contribute to its underuse or incomplete administration, as these deviations may undermine treatment efficacy and patient outcomes.
Questions/purposes: Among patients who met clear indications for rifampin use having undergone DAIR or one-stage revision for staphylococcal PJI, (1) what proportion of patients did not receive it? (2) What proportion of patients started it but did not complete the planned course? (3) Where documented in the medical record, what were the common reasons for not using it or prematurely discontinuing it, and in what percentage of the patients' charts was no reason given? (4) What proportion of patients were taking a medication that put them at risk for a drug-drug interaction (DDI)?
Methods: Using an institutional database, patients who underwent DAIR or revision arthroplasty for PJI from January 2013 to April 2023 were identified (n = 935).
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