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Therapeutic Drug Monitoring Jun 2022The objective of the present study was to determine the impact of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA). (Meta-Analysis)
Meta-Analysis
PURPOSE
The objective of the present study was to determine the impact of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA).
METHODS
PubMed, Embase, Web of Sciences, and Scopus were systematically searched to identify relevant studies reporting pharmacokinetic parameters [including trough concentration (C0), maximum concentration (Cmax), time to maximum concentration (Tmax), the dose-adjusted area under the concentration-time curve from time 0-12 hours (AUC0-12 h/D), and half-life (t1/2)], and pharmacodynamic outcomes of MPA (eg, acute graft rejection and adverse drug reactions), with and without PPI administration. Pooled effect estimates were calculated using a random-effects model.
RESULTS
Twelve studies involving 473 participants were eligible for inclusion, 11 of which were included in the meta-analysis. PPI exposure was significantly associated with lower C0 [mean difference (MD) = -0.62 mg/L; P = 0.003] lower Cmax (MD = -4.71 mg/L; P = 0.01), and longer Tmax (MD = 0.30 hours; P = 0.0001) of MPA. However, no significant association was observed between PPI exposure and AUC0-12 h/D, t1/2, or any pharmacodynamic outcomes. Based on subgroup analysis, it can be suggested that a significant association between PPI exposure and altered MPA pharmacokinetics was mainly associated with mycophenolate mofetil but not enteric-coated mycophenolate sodium.
CONCLUSIONS
Coadministration of PPIs and mycophenolate mofetil significantly altered the pharmacokinetics of MPA, particularly by decreasing MPA absorption. However, PPI-MPA interactions did not impact pharmacodynamic outcomes of MPA.
Topics: Area Under Curve; Drug Interactions; Graft Rejection; Humans; Immunosuppressive Agents; Mycophenolic Acid; Proton Pump Inhibitors
PubMed: 35239287
DOI: 10.1097/FTD.0000000000000947 -
Frontiers in Pharmacology 2024The recent exponential increase in legalized medical and recreational cannabis, development of medical cannabis programs, and production of unregulated over-the-counter...
BACKGROUND
The recent exponential increase in legalized medical and recreational cannabis, development of medical cannabis programs, and production of unregulated over-the-counter products (e.g., cannabidiol (CBD) oil, and delta-8-tetrahydrocannabinol (delta-8-THC)), has the potential to create unintended health consequences. The major cannabinoids (delta-9-tetrahydrocannabinol and cannabidiol) are metabolized by the same cytochrome P450 (CYP) enzymes that metabolize most prescription medications and xenobiotics (CYP3A4, CYP2C9, CYP2C19). As a result, we predict that there will be instances of drug-drug interactions and the potential for adverse outcomes, especially for prescription medications with a narrow therapeutic index.
METHODS
We conducted a systematic review of all years to 2023 to identify real world reports of documented cannabinoid interactions with prescription medications. We limited our search to a set list of medications with predicted narrow therapeutic indices that may produce unintended adverse drug reactions (ADRs). Our team screened 4,600 reports and selected 151 full-text articles to assess for inclusion and exclusion criteria.
RESULTS
Our investigation revealed 31 reports for which cannabinoids altered pharmacokinetics and/or produced adverse events. These reports involved 16 different Narrow Therapeutic Index (NTI) medications, under six drug classes, 889 individual subjects and 603 cannabis/cannabinoid users. Interactions between cannabis/cannabinoids and warfarin, valproate, tacrolimus, and sirolimus were the most widely reported and may pose the greatest risk to patients. Common ADRs included bleeding risk, altered mental status, difficulty inducing anesthesia, and gastrointestinal distress. Additionally, we identified 18 instances (58%) in which clinicians uncovered an unexpected serum level of the prescribed drug. The quality of pharmacokinetic evidence for each report was assessed using an internally developed ten-point scale.
CONCLUSION
Drug-drug interactions with cannabinoids are likely amongst prescription medications that use common CYP450 systems. Our findings highlight the need for healthcare providers and patients/care-givers to openly communicate about cannabis/cannabinoid use to prevent unintended adverse events. To that end, we have developed a free online tool (www.CANN-DIR.psu.edu) to help identify potential cannabinoid drug-drug interactions with prescription medications.
PubMed: 38868665
DOI: 10.3389/fphar.2024.1282831 -
Journal of the European Academy of... Jul 2023Skin barrier dysfunction plays an important role in atopic dermatitis (AD) aetiopathogenesis. Dupilumab, a drug that inhibits IL-4 and IL-13, is an effective treatment... (Review)
Review
Skin barrier dysfunction plays an important role in atopic dermatitis (AD) aetiopathogenesis. Dupilumab, a drug that inhibits IL-4 and IL-13, is an effective treatment for AD but there is scarce evidence about its impact on epidermal barrier. The objective of this systematic review is to evaluate the influence of dupilumab on skin barrier in patients with AD using non-invasive tools. A systematic review was designed following PRISMA guidelines. The literature search identified 73 references and, finally, only 6 were selected, including a total of 233 participants. All the studies were prospective observational studies. Dupilumab improved clinical scores in all the research. Skin barrier function parameters were mainly measured on the volar forearm. Transepidermal water loss (TEWL) was the parameter most frequently measured, evaluated in all the studies. Dupilumab decreased TEWL on eczematous lesions and non-involved skin. About 33.6% (2/6) studies reported that dupilumab also increased stratum corneum hydration (SCH) on eczematous lesions while one study did not report any changes in this parameter. This drug also decreased temperature and improved ceramide composition. In conclusion, dupilumab improved skin barrier function in AD patients, mainly reflected in a decreased in TEWL values.
Topics: Humans; Water Loss, Insensible; Skin; Dermatitis, Atopic; Epidermis; Observational Studies as Topic
PubMed: 36995919
DOI: 10.1111/jdv.19081 -
European Journal of Drug Metabolism and... Apr 2020Hepatic drug metabolism is a key influence on the efficacy and safety of medicines from both chemical and natural product sources. Studies of the metabolism of synthetic...
BACKGROUND AND OBJECTIVES
Hepatic drug metabolism is a key influence on the efficacy and safety of medicines from both chemical and natural product sources. Studies of the metabolism of synthetic compounds, herbal medicines/supplements, and herb-derived bioactive compounds are therefore challenging. The aim of the present review is to provide a summary of the approaches/techniques that are currently being employed to investigate different aspects of the metabolism of herbs and herb-derived compounds (reaction phenotyping, metabolite profiling, metabolic clearance prediction, metabolic/pharmacokinetic drug interactions, and metabolism-related pharmacokinetic studies), including their limitations.
METHODS
A thorough search of the PubMed database was performed using the terms 'Cancer' AND 'Cytochrome P450 (CYP)' OR 'Phase I metabolism' OR 'Phase II metabolism' AND 'Natural product' OR 'Herbal medicine' OR 'Herbal product' OR 'Herb-derived compound.'
RESULTS
Most of the studies (84 studies, 83.2%) retrieved during the search investigated metabolic/pharmacokinetic drug interactions. Three (3.0%), 7 (6.9%), 6 (5.9%), and 1 (1.0%) study involved metabolism-related pharmacokinetic studies, reaction phenotyping, metabolite profiling, and prediction of metabolic clearance, respectively.
CONCLUSIONS
Various studies reported conflicting results, with the results depending on the nature of the herb investigated (extracts or active constituents) and the biochemical tool (subcellular fractions, cells, or recombinant enzymes) and study system (in vitro/in vivo/ex vivo/clinical) applied. Each approach/system has its own advantages and disadvantages. Selecting the most appropriate approaches/systems allows us to extract the most meaningful and clinically relevant information on the metabolic pathways (the metabolites generated and the enzymes involved) and the potential drug interactions of herb-derived compounds for cancer therapy and prevention. Human primary hepatocytes are the best model that can be applied in any metabolic study. Human liver microsomes (HLMs) are a useful biochemical tool for preliminary drug metabolism studies. Recombinant microsomes that express specific enzymes and CYP-isoform-specific monoclonal antibodies are useful tools for enzyme inhibition studies.
Topics: Antineoplastic Agents, Phytogenic; Hepatocytes; Herb-Drug Interactions; Humans; Liver; Microsomes, Liver; Neoplasms; Plants, Medicinal
PubMed: 31679146
DOI: 10.1007/s13318-019-00582-8 -
Molecules (Basel, Switzerland) May 2022Bile acids (BAs) are important steroidal molecules with a rapidly growing span of applications across a variety of fields such as supramolecular chemistry, pharmacy, and... (Review)
Review
Bile acids (BAs) are important steroidal molecules with a rapidly growing span of applications across a variety of fields such as supramolecular chemistry, pharmacy, and biomedicine. This work provides a systematic review on their transport processes within the enterohepatic circulation and related processes. The focus is laid on the description of specific or less-specific BA transport proteins and their localization. Initially, the reader is provided with essential information about BAs' properties, their systemic flow, metabolism, and functions. Later, the transport processes are described in detail and schematically illustrated, moving step by step from the liver via bile ducts to the gallbladder, small intestine, and colon; this description is accompanied by descriptions of major proteins known to be involved in BA transport. Spillage of BAs into systemic circulation and urine excretion are also discussed. Finally, the review also points out some of the less-studied areas of the enterohepatic circulation, which can be crucial for the development of BA-related drugs, prodrugs, and drug carrier systems.
Topics: Bile Acids and Salts; Bile Ducts; Carrier Proteins; Enterohepatic Circulation; Liver
PubMed: 35566302
DOI: 10.3390/molecules27092961 -
Cardiovascular Drugs and Therapy Jun 2021Major depressive disorder (MDD) and anxiety disorders (AD) are both highly prevalent among individuals with arrhythmia, ischemic heart disease, heart failure,...
PURPOSE
Major depressive disorder (MDD) and anxiety disorders (AD) are both highly prevalent among individuals with arrhythmia, ischemic heart disease, heart failure, hypertension, and dyslipidemia. There should be increased support for MDD and AD diagnosis and treatment in individuals with cardiac diseases, because treatment rates have been low. However, cardiac-psychiatric drug interaction can make pharmacologic treatment challenging.
METHODS
The objective of the present systematic review was to investigate cardiac-psychiatric drug interactions in three different widely used pharmacological databases (Micromedex, Up to Date, and ClinicalKey).
RESULTS
Among 4914 cardiac-psychiatric drug combinations, 293 significant interactions were found (6.0%). When a problematic interaction is detected, it may be easier to find an alternative cardiac medication (32.6% presented some interaction) than a psychiatric one (76.9%). Antiarrhythmics are the major class of concern. The most common problems produced by these interactions are related to cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest), increased exposure of cytochrome P450 2D6 (CYP2D6) substrates, or reduced renal clearance of organic cation transporter 2 (OCT2) substrates and include hypertensive crisis, increased risk of bleeding, myopathy, and/or rhabdomyolysis.
CONCLUSION
Unfortunately, there is considerable inconsistency among the databases searched, such that a clinician's discretion and clinical experience remain invaluable tools for the management of patients with comorbidities present in psychiatric and cardiac disorders. The possibility of an interaction should be considered. With a multidisciplinary approach, particularly involving a pharmacist, the prescriber should be alerted to the possibility of an interaction. MDD and AD pharmacologic treatment in cardiac patients could be implemented safely both by cardiologists and psychiatrists.
TRIAL REGISTRATION
PROSPERO Systematic Review Registration Number: CRD42018100424.
Topics: Antipsychotic Agents; Cardiovascular Agents; Cardiovascular Diseases; Cytochrome P-450 CYP2D6; Databases, Pharmaceutical; Depressive Disorder, Major; Drug Interactions; Humans; Metabolic Clearance Rate; Organic Cation Transporter 2
PubMed: 32424652
DOI: 10.1007/s10557-020-06979-x -
Frontiers in Endocrinology 2022The objective of this systematic review is to synthesize the available evidence on the effectiveness of magnesium supplements on the markers of inflammation, oxidative...
The effect of magnesium alone or its combination with other supplements on the markers of inflammation, OS and metabolism in women with polycystic ovarian syndrome (PCOS): A systematic review.
UNLABELLED
The objective of this systematic review is to synthesize the available evidence on the effectiveness of magnesium supplements on the markers of inflammation, oxidative stress (OS), and metabolism in PCOS patients and to provide a basis for its clinical treatment. Electronic databases (PubMed, Cochrane Library databases, Embase, Web of science, CMB, CNKI, VIP, Wan Fang and ClinicalTrials.gov) were searched from their inception until January 2022. Randomized controlled trials (RCTs) for PCOS undergoing therapy with magnesium supplementation alone or in combination with other agents. The primary outcomes were the markers of blood glucose and OS.363 patients from nine RCTs were included in the current systematic review. Four of the nine studies reported the effects of magnesium supplementation alone on OS or metabolic markers in women with PCOS. Whilemagnesium supplementation alone did not show any significant improvement in the markers of inflammation, OS or metabolism in PCOS, seven of the nine articles reported the effect of magnesium co-supplementation on OS or metabolic markers in PCOS patients. Magnesium combined with vitamin E or zinc-calcium-vitamin D significantly improved glucose and lipid metabolism in PCOS patients. Magnesium intake alone did not lead to a significant improvement in the markers of OS, blood glucose, or serum lipids in PCOS. However, magnesium combined with other supplements (vitamin E, zinc, zinc-calcium-vitamin D) significantly improved serum hs-CRP, insulin, HOMA-IR, TG, TC levels, and the improvement in OS markers was inconclusive. The effect of magnesium and melatonin supplementation on the markers of metabolism needs to be further verified.
SYSTEM REVIEW REGISTRATION
PROSPERO https://www.crd.york.ac.uk/PROSPERO/#myprospero, CRD42022303410.
Topics: Biomarkers; Blood Glucose; Calcium; Dietary Supplements; Female; Humans; Inflammation; Magnesium; Oxidative Stress; Polycystic Ovary Syndrome; Vitamin D; Vitamin E; Zinc
PubMed: 35992132
DOI: 10.3389/fendo.2022.974042 -
Frontiers in Endocrinology 2023The aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic,... (Meta-Analysis)
Meta-Analysis Review
Effects of dietary polyphenol curcumin supplementation on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
The aim was to conduct a systematic review and meta-analysis for assessing the effectiveness and safety of dietary polyphenol curcumin supplement on metabolic, inflammatory, and oxidative stress indices in patients with metabolic syndrome (MetS).
METHODS
A comprehensive search for clinical trials was conducted in the following scientific databases: PubMed, SCOPUS, Cochrane Library, EMBASE, Web of Science, and China Biological Medicine. Randomized controlled trials (RCTs) evaluating the efficacy and safety of curcumin supplement for MetS were identified. A random-effects meta-analysis was performed using inverse variance, and efficacy was expressed as mean difference (MD) with 95% confidence interval (CI). The metabolic syndrome markers that were evaluated in the present study included waist circumference (WC), fasting blood sugar (FBS), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), C-reactive protein (CRP), ultrasensitive c-reactive protein (hsCRP), and malondialdehyde (MDA). By employing the Cochrane tool, RCTs were assessed for bias risk.
RESULTS
A total of 785 participants from 13 RCTs were included, with intervention durations ranging from 4 to 12 weeks. Compared with the control group, the curcumin group had positive effects on WC (MD = -2.16, 95% CI: -3.78 to -0.54, = 0.009, seven studies), FBS (MD = -8.6, 95% CI: -15.45 to -1.75, = 0.01, nine studies), DBP (MD = -2.8, 95% CI: -4.53 to - 1.06, = 0.002, five studies), HDL-C (MD = 4.98, 95% CI: 2.58 to 7.38, < 0.0001, eight studies), TNF-a (MD = -12.97, 95% CI: -18.37 to -7.57, < 0.00001, two studies), CRP (MD = - 1.24, 95% CI: -1.71 to -0.77, < 0.00001, two studies), and MDA (MD = -2.35, 95% CI: -4.47 to -0.24, = 0.03, three studies). These improvements were statistically significant. Meanwhile, there was no significant improvement in SBP (MD = -4.82, 95% CI: -9.98 to 0.35, = 0.07, six studies), TG (MD = 1.28, 95% CI: -3.75 to 6.30, = 0.62, eight studies), IL-6 (MD = -1.5, 95% CI: -3.97 to 0.97, = 0.23, two studies), or hsCRP (MD = -1.10, 95% CI: -4.35 to 2.16, < 0.51, two studies). FBS, SBP, HDL-C, IL-6, CRP, hsCRP, and MDA had a relatively high heterogeneity.
CONCLUSION
Curcumin exhibited promising potential in enhancing markers associated with metabolic syndrome, including inflammation. However, additional studies are required to confirm such findings since the included evidence is limited and has a relatively high heterogeneity.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022362553.
Topics: Randomized Controlled Trials as Topic; Curcumin; Dietary Supplements; Metabolic Syndrome; Oxidative Stress; Polyphenols; Inflammation; Humans; Curcuma
PubMed: 37522129
DOI: 10.3389/fendo.2023.1216708 -
Environmental and Molecular Mutagenesis Aug 2023Individual differences in drug response have always existed in clinical treatment. Many non-genetic factors show non-negligible impacts on personalized medicine.... (Review)
Review
Individual differences in drug response have always existed in clinical treatment. Many non-genetic factors show non-negligible impacts on personalized medicine. Emerging studies have demonstrated epigenetic could connect non-genetic factors and individual treatment differences. We used systematic retrieval methods and reviewed studies that showed individual factors' impact on DNA methylation of drug metabolism genes. In total, 68 studies were included, and half (n = 36) were cohort studies. Six aspects of individual factors were summarized from the perspective of personalized medicine: parental exposure, environmental pollutants exposure, obesity and diet, drugs, gender and others. The most research (n = 11) focused on ABCG1 methylation. The majority of studies showed non-genetic factors could result in a significant DNA methylation alteration in drug metabolism genes, which subsequently affects the pharmacokinetic processes. However, the underlying mechanism remained unknown. Finally, some viewpoints were presented for future research.
Topics: Humans; DNA Methylation; Epigenesis, Genetic; Diet
PubMed: 37522536
DOI: 10.1002/em.22567 -
European Journal of Clinical Nutrition May 2022Taurine (Tau) has modulatory effects on inflammatory and oxidative stress biomarkers; however, the results of clinical studies are not comprehensive enough to determine... (Meta-Analysis)
Meta-Analysis Review
Taurine (Tau) has modulatory effects on inflammatory and oxidative stress biomarkers; however, the results of clinical studies are not comprehensive enough to determine the effect of different durations and doses of Tau supplementation on inflammatory and oxidative stress biomarkers. The current study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. For this purpose, PubMed/Medline, Scopus, and Embase databases were systematically searched to obtain the relevant studies published before 30th March 2021. Meta-analysis was performed on controlled clinical trials by using the random-effects method. Non-linear relationship between variables and effect size was performed using dose-response and time-response analyses. The Cochrane Collaboration's tool was used to evaluate the quality of included studies. Tau supplementation can reduce the levels of malondialdehyde (MDA) (SMD = -1.17 µmol/l; 95% CI: -2.08, - 0.26; P = 0.012) and C-reactive protein (CRP) (SMD = -1.95 mg/l; 95% CI: -3.20, - 0.71; P = 0.002). There have been no significant effects of Tau supplementation on the levels of tumor necrosis factors-alpha (TNF-α) (SMD = -0.18 pg/ml; 95% CI: -0.56, 0.21; P = 0.368), and interleukin-6 (IL-6) (SMD = -0.49 pg/ml; 95% CI: -1.13, 0.16; P = 0.141). Besides, Tau has more alleviating effect on oxidative stress and inflammation on 56 days after supplementation (P < 0.05). Tau can decrease the levels of CRP and MDA. Based on the currently available evidence, Tau has no significant effect on the level of TNF-α and IL-6. Eight-week of Tau supplementation has more beneficial effects on inflammatory and oxidative stress biomarkers.
Topics: Biomarkers; C-Reactive Protein; Dietary Supplements; Humans; Inflammation; Interleukin-6; Oxidative Stress; Taurine; Tumor Necrosis Factor-alpha
PubMed: 34584225
DOI: 10.1038/s41430-021-01010-4