Current Drug Metabolism - Volume 26, Issue 3, 2025
Volume 26, Issue 3, 2025
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Unexpected Clinically Significant Drug-Drug Interaction between Tacrolimus and Metronidazole in the Early Period after Renal Transplantation: A Literature Review
More LessAuthors: Yun Xiao, Hua Zou, Xiaoyu Han, Chao Zheng, Chenglong Yin, Zhengyao Jiang, Sheng Zou, Anle Du, Na Deng, Guohui Li, Shuiwen Ye, Xiaohui Guo, Lin Zhong and Jiake HeIntroductionDrug interactions necessitate careful consideration in clinical practice. It is imperative for clinicians and pharmacists to monitor drug exposure and the co-administration of medications promptly in order to avert adverse outcomes and achieve optimal efficacy.
ObjectivesThe prevalence of oral lesions varies from 28% to 60% in the short term after renal transplantation. The clinical use of metronidazole in the treatment of anaerobic bacterial infections among solid organ transplant recipients has been complicated by the potentially significant and unpredictable drug-drug interactions.
MethodsWe present an unexpected clinically significant drug-drug interaction between tacrolimus and metronidazole in the early period after renal transplantation and describe the potential mechanism and clinical characteristics of this drug-drug interaction through a literature review.
ResultsA 34-year-old female experienced a 65% increase in dose-normalized tacrolimus trough concentration after intravenous administration of metronidazole at 1000 mg/day for 8 days. When metronidazole was switched from intravenous to oral for 5 days, dose-normalized tacrolimus trough concentration was still increased by 52.4%. The magnitude of tacrolimus-metronidazole drug-drug interaction seems to be contingent upon the dose of metronidazole and the route of metronidazole administration. After cessation of metronidazole for one month, this drug-drug interaction, as assessed by weight-normalized tacrolimus dose, may still persist.
ConclusionIn the early period following renal transplantation, the long-term concomitant use of metronidazole is likely to elevate the trough concentration of tacrolimus. Gene screening for CYP3A5*3/*3 and ABCB1 3435C>T in recipients of solid organ transplants may support individualized tacrolimus prescribing and facilitate the mitigation of risks associated with drug-drug interactions.
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Biopharmaceutical Factors Involved in the Disposition of Mycophenolic Acid: A Comprehensive Review of ADME Properties and Their Potential Impact on Mycophenolic Acid Plasma Exposure
More LessAuthors: Eric Asare, Ting Du, Huan Xie, Dong Liang and Song GaoMycophenolic acid (MPA) is an approved drug widely used as an immunosuppressant agent for the prevention of rejection in organ transplant patients and for managing various autoimmune disorders. Pharmacological studies have shown that the plasma exposure of MPA is critical to maintaining its efficacy, leading to a significant focus on MPA therapeutic drug monitoring (TDM) in clinical practice. Additionally, many papers have been published regarding MPA's absorption, distribution, metabolism, and elimination (ADME) characteristics, which are the key disposition factors affecting the plasma exposure of MPA. In this paper, we review the current data and information in the literature on the ADME properties of MPA and discuss their implications for MPA’s TDM. We also analyze the disposition of MPA major metabolites mycophenolic acid-glucuronide (MPAG), and acyl-glucuronide (AcMPAG), highlighting the key factors that affect MPA plasma exposure, including the influence of transporters, namely Multidrug Resistance-Associated Protein 2 (MRP2), Breast Cancer Resistance Protein (BCRP), Organic Anion-Transporting Polypeptides (OATPs), metabolic enzymes (i.e., UDP-Glucuronosyltransferases (UGTs)), enterohepatic recycling (EHR), and protein binding. We expect to provide researchers with a comprehensive understanding of factors that could affect MPA’s TDM to ensure its efficacy.
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Exploring the Effects of Oxidative Stress on Female Reproductive Function: The Role of Antioxidant Supplementation
More LessAuthors: Dala N. Daraghmeh, Sawsan Salameh, Massa Zahdeh, Rania Ghanem and Rafik KaramanBackgroundThe female reproductive system is susceptible to oxidative stress, which can interfere with ovulation, menstrual cycles, egg quality, and tubal function, ultimately leading to infertility. Antioxidants might play a crucial role in protecting reproductive health by neutralizing Reactive Oxygen Species (ROS) and preventing cellular damage.
ObjectiveTo provide an overview of the research that has been performed on the benefits of antioxidant supplementation for increasing female fertility.
MethodsWe conducted a comprehensive search of PubMed, Embase, and Google for full-text, English-language publications between 2000 and 2023 that investigated the relationship between antioxidant supplementation and improvements in female fertility.
ResultsAntioxidants have been investigated for their potential to improve fertility outcomes in subfertile women. Antioxidant supplementation shows promise in mitigating these effects by neutralizing excess ROS and restoring balance, leading to improved egg count and fertility outcomes. However, it is important to note that the effectiveness of antioxidant supplementation can vary depending on individual health factors and the specific antioxidants used. Studies suggest that a combination of antioxidants, such as vitamins C and E, selenium, and coenzyme Q10, may be more beneficial than single supplements. Although individual research has shown beneficial correlations between different antioxidant supplementation and female fertility, study repeatability is poor. As a result, further large-scale, well-designed clinical trials are necessary to better understand the precise role and optimal combinations of antioxidants for enhancing fertility in subfertile women.
Discussion and ConclusionThis review study offers crucial insights into the complex connection between OS and female reproductive health. It highlights the potential advantages of antioxidant supplements as a preventative strategy. To enhance female fertility outcomes, further research, particularly randomized controlled clinical trials, is needed to determine best practices, identify populations that could benefit the most, and explore innovative antioxidant treatments.
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Synthesis and Antimicrobial Activity of Silver/Copper Oxide/Clay Hybrid Nanocomposites Against Gram-Positive and Gram-Negative Bacteria
More LessBackgroundThe rapid surge in bacterial resistance to classical antibiotics and antimicrobial agents has driven researchers to identify new classes of antimicrobial agents. At the nanoscale, nanotechnological progress has strongly underscored the application of silver and copper since they present high antimicrobial activities toward gram-positive and gram-negative bacteria. Nanostructures containing these two elements-all the more so for hybrid nanocomposites—have been scantily the subject of investigated. The present work aims to develop and study a silver/copper oxide/clay hybrid nanocomposite.
MethodsNanocomposites of silver, copper oxide, and their hybrid with clay were synthesized via chemical precipitation under controlled pH (9-11) and temperature (60–90°C) conditions. The antibacterial activity was assessed using standard 0.5 McFarland-adjusted bacterial inocula. Characterization was performed using FTIR, XRD, FESEM, and TEM techniques. MIC and MBC were determined through serial dilution, and data were analyzed using one-way ANOVA and Tukey’s test (SPSS v26).
ResultsThe results indicated that the fabricated nanocomposite was impure, with nanosilver particles measuring 30–40 nm and copper oxide particles measuring 200–250 nm. The morphological properties of synthesized Ag/Cu2O/clay nanocomposites were evaluated using X-ray diffractometer analysis. The minimum inhibitory concentration (MIC) of the hybrid nanocomposite against Staphylococcus aureus and Bacillus subtilis was 1024 μg/ml, and for Escherichia coli and Pseudomonas aeruginosa 2048 μg/ml. The minimum bactericidal concentration (MBC) against Staphylococcus aureus and Bacillus subtilis was 4096 μg/ml, and for Escherichia coli 4096 μg/ml, and Pseudomonas aeruginosa 8192 μg/ml.
DiscussionSilver/copper oxide/clay hybrid nanocomposite exhibited more intensive antibacterial activities towards gram-positive bacteria in the absence of single-component nanocomposites, validating the synergistic effect of silver and copper in aid of clay. Its small efficacy on gram-negative strains also points at the necessity for additional optimization as well as extension. Such outcomes indicate the potential of the hybrid nanocomposite as an aspiring candidate for eventual antimicrobial applications.
ConclusionThese results showed that the antimicrobial property of silver/copper/clay hybrid nanocomposite was better than copper/silver and clay nanocomposite against gram-positive bacteria, while showing a similar effect against gram-negative bacteria.
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Influence of Orange Oil on Skin Permeability, Dermatokinetics, and In Vivo Anti-inflammatory Properties of Lornoxicam-loaded Niosomal Gel
More LessIntroductionLornoxicam is a non-steroidal anti-inflammatory drug belonging to the oxicam class. This study aimed to develop a niosomal gel containing orange oil for improving the anti-inflammatory effect of lornoxicam.
MethodsLornoxicam-loaded niosomes (LOR-OR-NIO) were prepared using film hydration followed by the sonication method. Particle size, entrapment efficiency, and ex vivo permeation were all considered during the optimization of the niosomal gels by employing the Box-Behnken design. Dermatokinetics and in vivo anti-inflammatory studies were performed using male Wistar rats.
ResultsThe particle size, entrapment efficiency, and skin permeation ability of the optimized LOR-OR-NIO formulation were found to be 354.3 nm, 83.56%, and 105.63 µg/cm2, respectively. The ex vivo studies indicated that the optimized LOR-OR-NIO gel demonstrated superior drug penetration properties (105.43 µg/cm2) compared to both the LOR-NIO gel (69.23 µg/cm2) and the LOR gel (35.34 µg/cm2). The activation energy values of LOR gel, LOR-NIO gel, and LOR-OR-NIO gel were 2.74 Kcal mol-1, 1.93 Kcal mol-1, and 0.94 Kcal mol-1, respectively.
DiscussionThe lower activation energy of the LOR-OR-NIO gel contributed to more skin penetration of the drug. Dermatokinetics investigation demonstrated that the LOR-OR-NIO gel had superior penetration in the epidermal and dermal areas compared to the LOR gel. In vivo anti-inflammatory studies indicated that the LOR-OR-NIO gel exhibited greater edema inhibition compared to both the LOR-NIO gel and LOR gel. These results demonstrated the enhanced anti-inflammatory activity of the LOR-OR-NIO gel.
Conclusion: The study concluded thatorange oil enhanced skin permeability and influenced the dermatokinetics of the LOR-OR-NIO gel, leading to an improvement in in vivo anti-inflammatory properties..
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Volumes & issues
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Volume 26 (2025)
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Volume 25 (2024)
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Volume 24 (2023)
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Volume 23 (2022)
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Volume 22 (2021)
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Volume 21 (2020)
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Volume 20 (2019)
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Volume 19 (2018)
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Volume 18 (2017)
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Volume 17 (2016)
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Volume 16 (2015)
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Volume 15 (2014)
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Volume 14 (2013)
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Volume 13 (2012)
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Volume 12 (2011)
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Volume 11 (2010)
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Volume 10 (2009)
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Volume 9 (2008)
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Volume 8 (2007)
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Volume 7 (2006)
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Volume 6 (2005)
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Volume 5 (2004)
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Volume 4 (2003)
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Volume 3 (2002)
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Volume 2 (2001)
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Volume 1 (2000)
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