Pharmacology Research & Perspectives最新文献

{"title":"Impact of a computerized physician order entry system on medication safety in pediatrics-The AVOID study.","authors":"Stefan Wimmer,&nbsp;Irmgard Toni,&nbsp;Sebastian Botzenhardt,&nbsp;Regina Trollmann,&nbsp;Wolfgang Rascher,&nbsp;Antje Neubert","doi":"10.1002/prp2.1092","DOIUrl":"https://doi.org/10.1002/prp2.1092","url":null,"abstract":"<p><strong>Background: </strong>One of the most critical steps in the medication process on pediatric wards is the medical prescription. This study aims to investigate the impact of a computerized physician order entry (CPOE) system on Adverse Drug Events (ADEs) and potentially harmful ADEs (pot ADEs) in comparison with paper-based documentation in a general pediatric ward at a German University hospital.</p><p><strong>Methods: </strong>A prospective pre-post study was conducted. All patients aged 17 years or younger were observed during the study periods (5 months pre- and postimplementation). Issues Regarding Medication (IRM) were identified by intensive chart review. Events were assessed regarding causality (WHO), severity (WHO; Dean & Barber for MEs), and preventability (Shumock) and classified into (pot) ADEs, (pot) Medication errors (ME), Adverse drug Reactions (ADR), and Other incidents (OI) accordingly.</p><p><strong>Results: </strong>Total of 333 patients with medication were included in the paper-based prescribing cohort (phase I) and 320 patients with medication in the electronic prescribing cohort (phase II). In each cohort, patients received a median number of four different drugs (IQR 5 and IQR 4). A total of 3966 IRM was observed. During the hospitalization, 2.7% (n = 9) patients in phase I and 2.8% (n = 9) in phase II experienced an ADE. Potentially harmful MEs were less often observed in the cohort with electronic prescribing (n = 228 vs. n = 562). The mean number per patient significantly decreased from 1.69 to 0.71 (p < .01).</p><p><strong>Conclusion: </strong>The implementation of a CPOE system resulted in a reduction of issues regarding medication, particularly MEs with the potential to harm patients decreased significantly.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/59/5a/PRP2-11-e01092.PMC10207936.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9875637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress in the adipose tissue and monocyte chemoattractant protein-1 are involved in tacrolimus-induced diabetes mellitus.","authors":"Xiaoxia Sun,&nbsp;Hongyang Wang,&nbsp;Jingwei Chi,&nbsp;Kui Che,&nbsp;Yangang Wang","doi":"10.1002/prp2.1081","DOIUrl":"https://doi.org/10.1002/prp2.1081","url":null,"abstract":"<p><p>Tacrolimus is an independent risk factor for new-onset diabetes after transplantation (NODAT). This study aimed to identify the mechanisms underlying tacrolimus-induced NODAT. About 80 kidney-transplant patients receiving tacrolimus were divided into NODAT and non-NODAT groups after 1 year. Binary logistic regression was used to identify risk factors for NODAT. Insulin resistance indices were estimated using the homeostasis model assessment. The blood levels of 13 adipocytokines were measured 1 week after transplantation. A tacrolimus-induced diabetes mouse model was used to reveal the underlying mechanisms. The cumulative NODAT incidence was 12.7% at 1 year (median, 6 months; range, 3-12 months). Tacrolimus trough levels ≥10 ng/mL during the first 3 months (odds ratio: 2.54, p = .012) were related to NODAT. Insulin resistance indices were higher in NODAT patients than in non-NODAT patients at 3, 6, and 12 months. Monocyte chemoattractant protein (MCP)-1 was overexpressed in blood in NODAT patients. In the animal experiments, postprandial blood glucose and insulin levels, insulin pathway protein levels in adipose tissue, MCP-1 expression in blood and adipose tissue, and number of macrophages in adipose tissue were markedly higher in tacrolimus-treated mice than in control mice, and these increases were dose-dependent. The expression of endoplasmic reticulum (ER) stress proteins in adipose tissue was increased in a tacrolimus dose-dependent manner. In conclusion, tacrolimus-induced insulin resistance. Tacrolimus trough levels ≥10 ng/mL during the first 3 postoperative months were an independent risk factor for NODAT. ER stress and MCP-1 underlie tacrolimus-induced diabetes.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/fa/PRP2-11-e01081.PMC10190605.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9513647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational design and molecular modeling of morphine derivatives for preferential binding in inflamed tissue.","authors":"Makena Augenstein,&nbsp;Nayiri Alexander,&nbsp;Matthew Gartner","doi":"10.1002/prp2.1075","DOIUrl":"https://doi.org/10.1002/prp2.1075","url":null,"abstract":"<p><p>The opioid epidemic has impacted over 10 million Americans in 2019. Opioids, like morphine, bind non-selectively in both peripheral tissue, leading to effective pain relief, and central tissue, resulting in dangerous side effects and addiction. The inflamed conditions of injured tissues have a lower pH (pH = 6-6.5) environment than healthy tissue (pH = 7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using molecular extension and dissection techniques. Morphine binds to the μ-opioid receptor (MOR) when the biochemically active amine group is protonated. Fluorination of a β-carbon from the tertiary amine group led to a reduced pKa of the derivative through induction. Through a decrease in the pKa, protonation is still statistically favored in lower pH environments of inflamed tissue but primarily deprotonated in healthy tissue. The cyclohexenol and N-methyl-piperidine rings of morphine are removed to increase conformational flexibility when binding while still maintaining the interactions required for analgesia. Electronic structure calculations were performed with Gaussian16 using the Keck Computational Research Cluster at Chapman University to determine the pKa. The theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate the ΔG°aq values for the amine deprotonation reactions. Fluoromorphine β-C2 was designed computationally and modeled within the MOR using Maestro: Schrödinger. This derivative exhibits a pKa reduction and enhanced ligand-protein interactions within the MOR. β-fluorination decreased the overall pKa values of the morphine derivatives (pKa: 6.1-7.83) relative to morphine, reducing binding within healthy, central tissue.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/00/PRP2-11-e01075.PMC10116396.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9442086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma concentration of atorvastatin metabolites correlates with low-density lipoprotein cholesterol reduction in patients with coronary heart disease.","authors":"E Sverre,&nbsp;J Munkhaugen,&nbsp;O Kristiansen,&nbsp;H Weedon-Fekjaer,&nbsp;K Peersen,&nbsp;E Gjertsen,&nbsp;L Gullestad,&nbsp;S Bergan,&nbsp;E Husebye,&nbsp;N T Vethe","doi":"10.1002/prp2.1089","DOIUrl":"https://doi.org/10.1002/prp2.1089","url":null,"abstract":"<p><p>In this exploratory study from a randomized double-blinded crossover trial including 70 patients with coronary heart disease and self-perceived muscular side effects of statins, we aimed to determine the relationship between low-density lipoprotein cholesterol (LDL-C) reduction and atorvastatin metabolite plasma concentrations. All patients underwent a 7 weeks treatment period with atorvastatin 40 mg/day and a 7 weeks placebo period in random order. Nonlinear regression with a three-parameter equation explored the relationship between percentage LDL-C reduction (statin vs. placebo) and the pharmacokinetic variables. Mean LDL-C reduction was 49% (range 12% to 71%). The sum of 4-OH-atorvastatin acid and lactone correlated moderately with the LDL-C response (Spearman ρ 0.27, 95% confidence interval [CI]: 0.03 to 0.48). Accordingly, nonlinear regression showed R² of 0.14 (95% CI: 0.03 to 0.37, R² adjusted equaled 0.11). Even a perfect underlying correlation of 1.0 showed R²  = 0.32 by simulation, using historical intra-individual LDL-C variation (8.5%). The 90% inhibitory concentration was 2.1 nmol/L, and the 4-OH-metabolite sum exceeded this threshold in 34% of the patients. In conclusion, trough plasma concentrations of 4-OH-atorvastatin metabolites correlated moderately to the LDL-C reduction. A plateau LDL-C response was observed above a pharmacokinetic threshold, below which the response was highly variable. The usefulness of monitoring concentrations of atorvastatin metabolites to optimize the individual dosage have limitations, but its supportive potential may be pursued in relevant patient subsets to achieve adequate efficacy at the lowest possible dose. The results add knowledge to the overall understanding of the variable LDL-C response mediated by atorvastatin.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/aa/88/PRP2-11-e01089.PMC10131217.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9514662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Australian pharmacists' views toward reducing the risk of medicines-related harm in aged care residents.","authors":"Sheraz Ali,&nbsp;Colin M Curtain,&nbsp;Gregory M Peterson,&nbsp;Mohammed S Salahudeen","doi":"10.1002/prp2.1104","DOIUrl":"https://doi.org/10.1002/prp2.1104","url":null,"abstract":"<p><p>Medicines-related harm is common in older people living in residential aged care facilities (RACFs). Pharmacists offering services in the aged care sector may play a key role in reducing medicines-related injury. This study aimed to explore Australian pharmacists' views toward reducing the risk of medicines-related harm in older residents. Qualitative, semi-structured interviews were conducted with 15 Pharmacists across Australia providing services (e.g., through the provision of medication reviews, supplying medications, or being an embedded pharmacist) to RACFs identified via convenience sampling. Data were analyzed by thematic analysis using an inductive approach. Medicines-related harm was thought to occur due to polypharmacy, inappropriate medicines, anticholinergic activity, sedative load, and lack of reconciliation of medicines. Pharmacists reported that strong relationships, education of all stakeholders, and funding for pharmacists were facilitators in reducing medicines-related harm. Pharmacists stated that renal impairment, frailty, staff non-engagement, staff burnout, family pressure, and underfunding were barriers to reducing medicines-related harm. Additionally, the participants suggested pharmacist education, experience, and mentoring improve aged care interactions. Pharmacists believed that the irrational use of medicines increases harm in aged care residents, and medicines-specific (e.g., sedative load) and patient-specific risk factors (e.g., renal impairment) are associated with injuries in residents. To reduce medicines-related harm, the participants highlighted the need for increased funding for pharmacists, improving all stakeholders' awareness about medicines-associated harms through education, and ensuring collaboration between healthcare professionals caring for older residents.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10207935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9875635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapamycin treatment increases survival, autophagy biomarkers and expression of the anti-aging klotho protein in elderly mice.","authors":"Kitti Szőke,&nbsp;Beáta Bódi,&nbsp;Zoltán Hendrik,&nbsp;Attila Czompa,&nbsp;Alexandra Gyöngyösi,&nbsp;Donald David Haines,&nbsp;Zoltán Papp,&nbsp;Árpád Tósaki,&nbsp;István Lekli","doi":"10.1002/prp2.1091","DOIUrl":"https://doi.org/10.1002/prp2.1091","url":null,"abstract":"<p><p>Previous investigations have demonstrated that treatment of animals with rapamycin increases levels of autophagy, which is a process by which cells degrade intracellular detritus, thus suppressing the emergence of senescent cells, whose pro-inflammatory properties, are primary drivers of age-associated physical decline. A hypothesis is tested here that rapamycin treatment of mice approaching the end of their normal lifespan exhibits increased survival, enhanced expression of autophagic proteins; and klotho protein-a biomarker of aging that affects whole organism senescence, and systemic suppression of inflammatory mediator production. Test groups of 24-month-old C57BL mice were injected intraperitoneally with either 1.5 mg/kg/week rapamycin or vehicle. All mice administered rapamycin survived the 12-week course, whereas 43% of the controls died. Relative to controls, rapamycin-treated mice experienced minor but significant weight loss; moreover, nonsignificant trends toward decreased levels of leptin, IL-6, IL-1β, TNF-α, IL-1α, and IGF-1, along with slight elevations in VEGF, MCP-1 were observed in the blood serum of rapamycin-treated mice. Rapamycin-treated mice exhibited significantly enhanced autophagy and elevated expression of klotho protein, particularly in the kidney. Rapamycin treatment also increased cardiomyocyte Ca²⁺ -sensitivity and enhanced the rate constant of force re-development, which may also contribute to the enhanced survival rate in elderly mice.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b1/90/PRP2-11-e01091.PMC10185870.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9520435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The influence of SARS-CoV-2 infection on expression of drug-metabolizing enzymes and transporters in a hACE2 murine model.","authors":"Kiran Deshpande, Keith R Lange, William B Stone, Christine Yohn, Naomi Schlesinger, Leonid Kagan, Albert J Auguste, Bonnie L Firestein, Luigi Brunetti","doi":"10.1002/prp2.1071","DOIUrl":"10.1002/prp2.1071","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting Coronavirus disease 2019 emerged in late 2019 and is responsible for significant morbidity and mortality worldwide. A hallmark of severe COVID-19 is exaggerated systemic inflammation, regarded as a \"cytokine storm,\" which contributes to the damage of various organs, primarily the lungs. The inflammation associated with some viral illnesses is known to alter the expression of drug-metabolizing enzymes and transporters. These alterations can lead to modifications in drug exposure and the processing of various endogenous compounds. Here, we provide evidence to support changes in the mitochondrial ribonucleic acid expression of a subset of drug transporters (84 transporters) in the liver, kidneys, and lungs and metabolizing enzymes (84 enzymes) in the liver in a humanized angiotensin-converting enzyme 2 receptor mouse model. Specifically, three drug transporters (Abca3, Slc7a8, Tap1) and the pro-inflammatory cytokine IL-6 were upregulated in the lungs of SARS-CoV-2 infected mice. We also found significant downregulation of drug transporters responsible for the movement of xenobiotics in the liver and kidney. Additionally, expression of cytochrome P-450 2f2 which is known to metabolize some pulmonary toxicants, was significantly decreased in the liver of infected mice. The significance of these findings requires further exploration. Our results suggest that further research should emphasize altered drug disposition when investigating therapeutic compounds, whether re-purposed or new chemical entities, in other animal models and ultimately in individuals infected with SARS-CoV-2. Moreover, the influence and impact of these changes on the processing of endogenous compounds also require further investigation.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/4d/PRP2-11-e01071.PMC10155506.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survey analysis and discussion on cultivating scientific research quality among undergraduates in medical colleges.","authors":"Ling Liu,&nbsp;Jing Luan","doi":"10.1002/prp2.1095","DOIUrl":"https://doi.org/10.1002/prp2.1095","url":null,"abstract":"<p><p>To explore rational measures to improve medical undergraduates' scientific research quality by investigating and analyzing their scientific research situation. A questionnaire survey was conducted in March 2022 among medical college/university undergraduates across four grades and five majors. Five hundred and ninety-four questionnaires were distributed, and 553 valid copies were returned, with a 93.1% return rate. The results showed that 61.5% of the students had an intense interest in research experiments, and 46.8% thought it was important for undergraduates to participate in research experiments, but only 17.5% often participated in them. Among the students, 85.0% thought that the main factors preventing them from participating in research experiments were academic stress and insufficient time, and 82.6% hoped that mentors would focus on practical skills training; only 13.0% read literature at least once per week, and 93.5% were not proficient at organizing and using literature. Among the participating undergraduates, more than half were strongly interested in scientific research, but academic stress, unclear participation modes, and insufficient literature retrieval skills limited undergraduate scientific research practice and improvement of scientific quality. Therefore, it is essential to cultivate undergraduates' interest in scientific research, ensure that they have spare time to engage in scientific research, improve the undergraduate scientific research mentorship system, and enhance relevant scientific research abilities to cultivate more innovative talent in scientific research.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9508454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"JP-1366: A novel and potent potassium-competitive acid blocker that is effective in the treatment of acid-related diseases.","authors":"Jin Mo Ku,&nbsp;Jin Hee Cho,&nbsp;Kangjeon Kim,&nbsp;Ji Yoon Kim,&nbsp;Jong Yup Kim,&nbsp;John Kim,&nbsp;Hyunju Cha,&nbsp;Banyoon Cheon","doi":"10.1002/prp2.1090","DOIUrl":"https://doi.org/10.1002/prp2.1090","url":null,"abstract":"<p><p>The global prevalence of GERD is substantially increasing each year, and GERD is a chronic disease that reduces the quality of life of patients. The efficacy of conventional drugs is diverse, and most require long-term or lifetime administration; thus, the development of more effective therapeutic agents is needed. Herein, a more effective treatment for GERD was tested. We investigated whether JP-1366 affected gastric H+/K+-ATPase activity and used the Na+/K+-ATPase assay to confirm the selectivity of H+/K+-ATPase inhibition. To clarify the mechanism of enzyme inhibition, JP-1366 and TAK-438 were analyzed by Lineweaver-Burk. Also, we investigated the effects of JP-1366 in various models involving reflux esophagitis. We found that JP-1366 mediates strong, selective, and dose-dependent inhibition of H+/K+-ATPase. We found that JP-1366 significantly suppressed gastric acid secretion in histamine-treated pylorus-ligated rats in a dose-dependent manner. Additionally, we confirmed that JP-1366 inhibited histamine-stimulated gastric acid secretion in the HPD model. JP-1366 exhibited a more than 2-fold higher inhibitory effect on esophageal injury than TAK-438 in GERD lesions and had a more potent inhibitory effect in indomethacin- or aspirin-induced gastric ulcer rat models than TAK-438. Additionally, JP-1366 inhibited gastric ulcers. These results support the possibility that JP-1366 is a good candidate drug for treating acid-related diseases.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/33/ad/PRP2-11-e01090.PMC10163344.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral antibiotics lower mycophenolate mofetil drug exposure, possibly by interfering with the enterohepatic recirculation: A case series.","authors":"Mirjam Simoons,&nbsp;Kishan A T Naipal,&nbsp;Huib de Jong,&nbsp;Caroline M den Hoed,&nbsp;Brenda C M de Winter,&nbsp;Midas B Mulder","doi":"10.1002/prp2.1103","DOIUrl":"https://doi.org/10.1002/prp2.1103","url":null,"abstract":"<p><p>Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant recipients. Exposure to the active mycophenolic acid (MPA) can be monitored using therapeutic drug monitoring. We present three cases in which MPA exposure severely decreased after oral antibiotic coadministration. By diminishing gut bacteria β-glucuronidase activity, oral antibiotics can prevent deglucuronidation of the inactive MPA-7-O-glucuronide metabolite to MPA and thereby possibly prevent its enterohepatic recirculation. This pharmacokinetic interaction could result in rejection, which makes it clinically relevant in solid organ transplant recipients, especially when therapeutic drug monitoring frequency is low. Routine screening for this interaction, preferably supported by clinical decision support systems, and pragmatic close monitoring of the MPA exposure in cases is advised.</p>","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/cc/PRP2-11-e01103.PMC10207934.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9875636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}