-
Journal of Cardiology Jun 2019Amiodarone, which inhibits CYP2C9 and P-glycoprotein, is commonly prescribed with non-vitamin K antagonist oral anticoagulants (NOACs) and polypharmacy in high-risk... (Meta-Analysis)
Meta-Analysis
Non-vitamin K antagonist oral anticoagulants with amiodarone, P-glycoprotein inhibitors, or polypharmacy in patients with atrial fibrillation: Systematic review and meta-analysis.
BACKGROUND
Amiodarone, which inhibits CYP2C9 and P-glycoprotein, is commonly prescribed with non-vitamin K antagonist oral anticoagulants (NOACs) and polypharmacy in high-risk atrial fibrillation (AF) patients. We studied efficacy and safety of NOACs in AF patients receiving amiodarone, P-glycoprotein inhibitor, or polypharmacy.
METHODS
After a systematic database search (Medline, EMBASE, CENTRAL, SCOPUS, and Web of Science), four phase-III randomized trials comparing NOACs and warfarin in "with/without amiodarone," "with/without P-glycoprotein inhibitors," or "with/without multiple (≥5, polypharmacy) concomitant drugs" subgroups were included. The outcomes were pooled using a random-effects model to determine the relative risks (RRs) for stroke/systemic thromboembolism (SSTE), major bleeding (MB), intracranial hemorrhage (ICH), and all-cause mortality.
RESULTS
Among patients taking amiodarone, superiority of NOACs over warfarin in non-amiodarone users disappeared in terms of SSTE (p=0.11), MB (p=0.95), ICH (p=0.26), and mortality (p=0.32). No safety benefit (MB) of NOACs compared to warfarin was shown in patients taking P-glycoprotein inhibitors (p=0.47), but SSTE prevention was still superior with NOACs compared to warfarin in the same patient group [RR=0.78 (0.61-0.99), p=0.04, I=11%]. In AF patients with polypharmacy, NOACs showed a lower risk of SSTE [RR=0.82 (0.71-0.96), p=0.01, I=0%] and mortality [RR=0.91 (0.83-0.99), p=0.04, I=0%], but not MB (p=0.81) compared to warfarin.
CONCLUSIONS
NOACs were equivalent to warfarin among AF patients with concomitant amiodarone use in terms of efficacy, safety, and mortality. There was no safety benefit of NOACs over warfarin in patients using polypharmacy or P-glycoprotein inhibitors.
SYSTEMATIC REVIEW REGISTRATION
The protocol of this meta-analysis was registered on PROSPERO under CRD42018104808 (https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42018104808).
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Administration, Oral; Adult; Aged; Amiodarone; Anticoagulants; Atrial Fibrillation; Clinical Trials, Phase III as Topic; Female; Hemorrhage; Humans; Male; Middle Aged; Polypharmacy; Randomized Controlled Trials as Topic; Stroke; Thromboembolism; Treatment Outcome
PubMed: 30770140
DOI: 10.1016/j.jjcc.2018.12.018 -
Oxidative Medicine and Cellular... 2016Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia... (Review)
Review
Cancer is a leading cause of death worldwide. We aim to provide a systematic review about the roles of reactive oxygen species (ROS) in anticancer therapy with Salvia miltiorrhiza Bunge (Danshen). Danshen, including its lipophilic and hydrophilic constituents, is potentially beneficial for treating various cancers. The mechanisms of ROS-related anticancer effects of Danshen vary depending on the specific type of cancer cells involved. Danshen may enhance TNF-α-induced apoptosis, upregulate caspase-3, caspase-8, caspase-9, endoplasmic reticulum stress, P21, P53, Bax/Bcl-2, DR5, and AMP-activated protein kinase, or activate the p38/JNK, mitogen-activated protein kinase, and FasL signaling pathways. Conversely, Danshen may downregulate human telomerase reverse transcriptase mRNA, telomerase, survivin, vascular endothelial growth factor/vascular endothelial growth factor receptor 2, CD31, NF-κB, Erk1/2, matrix metalloproteinases, microtubule assembly, and receptor tyrosine kinases including epidermal growth factor receptors, HER2, and P-glycoprotein and inhibit the PI3K/Akt/mTOR or estrogen receptor signaling pathways. Therefore, Danshen may inhibit cancer cells proliferation through antioxidation on tumor initiation and induce apoptosis or autophagy through ROS generation on tumor progression, tumor promotion, and tumor metastasis. Based on the available evidence regarding its anticancer properties, this review provides new insights for further anticancer research or clinical trials with Danshen.
Topics: Animals; Antineoplastic Agents; Drugs, Chinese Herbal; Humans; Hydrophobic and Hydrophilic Interactions; Neoplasms; Reactive Oxygen Species; Salvia miltiorrhiza
PubMed: 27579153
DOI: 10.1155/2016/5293284 -
Asian Pacific Journal of Cancer... 2014The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated to influence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. This meta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and the risk of gastric cancer (GC) and peptic ulcer (PU).
MATERIALS AND METHODS
A literature search was conducted with PubMed, Embase and the Cochrane library up to November 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Data were analyzed using Review Manager (Version 5.2), and Stata package (version 12.0) for estimation of publication bias.
RESULTS
Six case-control studies were included, of which five were for GC and two for PU. Overall, no evidence was found for any association between the MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pylori infection status, stage and histology classification of GC, and PU type, there was still no significant association between them.
CONCLUSIONS
This meta-analysis suggested that the MDR1 C3435T polymorphism is not associated with susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carcinogenesis; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Peptic Ulcer; Polymorphism, Single Nucleotide; Stomach Neoplasms
PubMed: 24815441
DOI: 10.7314/apjcp.2014.15.7.3021 -
PloS One 2014Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse. (Meta-Analysis)
Meta-Analysis Review
Impact of ABCB1 and CYP2B6 genetic polymorphisms on methadone metabolism, dose and treatment response in patients with opioid addiction: a systematic review and meta-analysis.
BACKGROUND
Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse.
OBJECTIVES
To determine whether the CYP2B6*6 or ABCB1 (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment).
METHODS
Two independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science databases. We included studies that reported methadone plasma concentration, methadone response, or methadone dose in relation to the CYP2B6*6 or ABCB1 polymorphisms.
RESULTS
We screened 182 articles and extracted 7 articles for inclusion in the meta-analysis. Considerable agreement was observed between the two independent raters on the title (kappa, 0.82), abstract (kappa, 0.43), and full text screening (kappa, 0.43). Trough (R) methadone plasma concentration was significantly higher in CYP2B6*6 homozygous carriers when compared to non-carriers (standardized mean difference [SMD] = 0.53, 95% confidence interval [CI], 0.05-1.00, p = 0.03) with minimal heterogeneity (I(2) = 0%). Similarly, trough (S) methadone plasma concentration was higher in homozygous carriers of the *6 haplotype when compared to non-carriers, (SMD = 1.44, 95% CI 0.27-2.61, p = 0.02) however significant heterogeneity was observed (I(2) = 69%). Carriers of the CYP2B6*6 haplotype were not found to be significantly different from non-carriers with respect to dose or response to treatment. We found no significant association between the ABCB1 polymorphism and the trough (R), (S) plasma concentrations, methadone dose, or methadone response.
CONCLUSION
Although the number of studies included and sample size were modest, this is the first meta analysis to show participants homozygous for the CYP2B6*6 genotype have higher trough (R) and (S) methadone plasma concentrations, suggesting that methadone metabolism is significantly slower in *6 homozygous carriers.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Analgesics, Opioid; Aryl Hydrocarbon Hydroxylases; Biotransformation; Cytochrome P-450 CYP2B6; Databases, Bibliographic; Drug Administration Schedule; Drug Monitoring; Haplotypes; Homozygote; Humans; Methadone; Opioid-Related Disorders; Polymorphism, Genetic
PubMed: 24489693
DOI: 10.1371/journal.pone.0086114 -
Cancer Cell International May 2013The multidrug resistance (MDR) 1 gene encodes a 170-kDa membrane transporter called P-glycoprotein, which plays an important role in protecting cells against lipophilic...
BACKGROUND
The multidrug resistance (MDR) 1 gene encodes a 170-kDa membrane transporter called P-glycoprotein, which plays an important role in protecting cells against lipophilic xenobiotics by the way of an ATP-dependent cellular efflux mechanism. Three polymorphisms of MDR1, 3435C > T located in exon 26, 1236C > T in exon 12 and 2677G > T/A in exon 21 were the most extensively studied and were identified functionally important and ethnically diverse mapping to the gene region. Considering the potential influence of altering MDR1 activity, it is plausible that MDR1 polymorphisms might play a role in the development of cancer. Although the effects of MDR1 polymorphisms on susceptibility to human cancer have been investigated in many studies, the results still remain conflicting.
METHODS
To resolve these conflicts, we performed a quantitative synthesis of the association between these three polymorphisms and cancer risk, including 52 studies (15789 cases and 20274 controls) for 3435C > T polymorphism, 10 studies (2101 cases and 2842 controls) for 1236C > T polymorphism and 18 studies (3585 cases and 4351 controls) for 2677G > T/A polymorphism.
RESULTS
The stratified analyses for 3435C > T polymorphism, individuals with T-allele in 3435C > T had significantly higher ALL risks (TT versus CC: OR =1.286, 95% CI =1.123-1.474); significantly elevated risks were observed among Caucasian populations (TT versus CC: OR =1.276, 95% CI =1.112-1.464). When restricting the analysis to the source of controls, we found that HB (hospital-based) genetic models had higher risks (TT versus CC: OR =1.307, 95% CI =1.046-1.632), as well as in PB (population-based) genetic models (TT versus CC: OR =1.294, 95% CI =1.079-1.55).The T/A-allele frequency of 2677G > T/A polymorphism was associated with higher risk of cancer (TT + TA + AA vs. GG: OR =1.348, 95% CI =1.031-1.762), significantly elevated risks were observed among Asian populations (TT + TA + AA vs. GG: OR =1.642, 95% CI =1.340-2.012), and elevated risks could be associated with PB models (TT + TA + AA vs. GG: OR =1.641, 95% CI =1.018-2.646).
CONCLUSIONS
Our meta-analysis suggested that 3435C > T polymorphism and 2677G > T/A polymorphism were associated with cancer risk when all studies were pooled together, while 1236C > T polymorphism not.
PubMed: 23687985
DOI: 10.1186/1475-2867-13-46 -
Farmacia Hospitalaria : Organo Oficial... 2012The new protease inhibitors (PIs), telaprevir and boceprevir, with peginterferon and ribavirin, have increased the response rate in patients with genotype 1 chronic... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The new protease inhibitors (PIs), telaprevir and boceprevir, with peginterferon and ribavirin, have increased the response rate in patients with genotype 1 chronic hepatitis C. Both are metabolized by CYP3A and they are CYP3A inhibitors. Furthermore, they are substrates, also telaprevir is an inhibitor, for P-glycoprotein. Our aim is to analyze the interactions between these IPs and other medications.
METHOD
We performed a systematic review in PubMed and Cochrane database and in conference abstracts of the last 2-5 years. Another search was performed in Medline to check efficacy clinical trials in phase II and III, in Micromedex database and in label information.
RESULTS
In PubMed we found two Phase I clinical trials; we did not find any article in the Cochrane database. 14 conference abstracts were selected, mainly there are phase I studies. In the free search in PubMed was located an in vitro / in vivo preclinical study which analyzed the co-administration of IPs and ritonavir. In phase II and III clinical trials, there was no mention about interactions.
CONCLUSIONS
Currently, there are pharmacokinetic Phase I studies about the interaction between PIs and representative drugs (potent inducers, potent inhibitors, high protein binding drugs, etc.), but the evidence of these interactions is contradictory. Its incorporation into the therapeutic have to take into account the possibility of complex interactions and not entirely known, about their mechanism of action, which might compromise its effectiveness or increase its toxicity.
Topics: Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Interactions; HIV Protease Inhibitors; Hepatitis C, Chronic; Humans; Oligopeptides; Proline
PubMed: 23461440
DOI: 10.7399/FH.2012.36.6.47 -
Planta Medica Sep 2012The use of herbal/botanical products, also referred to as complementary and alternative medicines (CAM), worldwide enjoys increasing popularity. It appears in particular... (Review)
Review
The use of herbal/botanical products, also referred to as complementary and alternative medicines (CAM), worldwide enjoys increasing popularity. It appears in particular highly prevalent in patient populations already exposed to complex treatment algorithms and polypharmacotherapy, frequently involving narrow therapeutic index drugs. Accordingly, the potential clinical dimension and relevance of herb-drug interactions has received considerable attention over the last years. However, review of pertinent literature indicates that the available clinical evidence in this regard is still limited and sometimes inconclusive. Also, communication of herb-drug interaction data in the biopharmaceutical/medical literature is often complex and confusing, not always unbiased, and in many cases appears not to strive for clear-cut and useful guidance in terms of the clinical relevance of such findings.This systematic review summarizes and interprets the published evidence on clinical herb-drug interaction studies which examined the potential of six popular herbal drugs (Echinacea, garlic, gingko, ginseng, goldenseal, and milk thistle) as perpetrators of pharmacokinetic (PK) drug interactions. Reported effect sizes were systematically categorized according to FDA drug interaction guideline criteria. A total of 66 clinical PK interaction studies, meeting the scope of the present review, were identified. The clinical evidence was found to be most robust and informative for Gingko biloba (GB; 21 studies) and milk thistle/silymarin (MT; 13), and appears still limited for ginseng (9), goldenseal/berberine (GS; 8), garlic (8), and Echinacea (7). Collectively, the available evidence indicates that, at commonly recommended doses, none of these herbs act as potent or moderate inhibitors or inducers of cytochrome P450 (CYP) enzymes or P-glycoprotein (ABCB1). Weak effects in terms of either induction or inhibition were found for GB (presystemic/hepatic CYP3A4 induction/inhibition, CYP2C19 induction at high doses), milk thistle/silymarin (CYP2C9 inhibition), GS/berberine (CYP3A4 and CYP2D6 inhibition), Echinacea (presystemic/hepatic CYP3A4 inhibition/induction, CYP1A2 and CYP2C9 inhibition at high doses). Information was found not always complete for the major drug metabolizing CYP enzymes in the less well-studied herbs and is largely limited to P-glycoprotein (ABCB1) when effects on drug transporters have been investigated.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cytochrome P-450 Enzyme System; Echinacea; Garlic; Ginkgo biloba; Herb-Drug Interactions; Humans; Hydrastis; Silybum marianum; Panax; Pharmacokinetics; Plant Preparations
PubMed: 22855269
DOI: 10.1055/s-0032-1315117 -
Seizure Jul 2010The C3435T, a major allelic variant of the ABCB1 gene, is proposed to play a crucial role in drug-resistance in epilepsy. The C/C genotype carriers reportedly are at... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The C3435T, a major allelic variant of the ABCB1 gene, is proposed to play a crucial role in drug-resistance in epilepsy. The C/C genotype carriers reportedly are at higher risk of pharmacoresistance to AEDs, but only in some studies. The hypothesis of the C-variant associated risk and resistance to antiepileptic drugs (AEDs) has been hampered by conflicting results from inadequate power in case-control studies. To assess the role of C3435T polymorphism in drug-resistance in epilepsy, a systematic review and meta-analysis was conducted.
METHODS
Databases were obtained from the Cochrane Library, MEDLINE, EMBASE, major American and European conference abstracts, and www.google.my for genetic association studies up to February 2010. All the case-control association studies evaluating the role of ABCB1 C3435T in pharmacoresistance to AEDs were identified. The new definition of treatment outcome from International League Against Epilepsy (ILAE) was used for including studies for sub-analysis. To measure the strength of genetic association for the gene variant, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using models of both fixed- and random-effects for comparisons of the alleles and genotypes with co-dominant (C/C vs. T/T, C/T vs. T/T), dominant (C/C+C/T vs. T/T), and recessive (C/C vs. C/T+T/T) models in overall and in ethnicity subgroups. The 19 studies were selected for the next sub-analysis based on the new definition of drug-responsiveness and drug-resistance from ILAE. The same analysis was also performed for treatment outcome and ethnicity subgroups.
RESULTS
A total of 22 association studies including 3231 (47.8%) drug-resistant patients and 3524 (52.2%) drug-responsive patients or healthy controls (genotyped for C3435T) were pooled in this meta-analysis. The allelic association of ABCB1 C3435T with risk of drug-resistance was not significant under fixed-effects model, 1.06 (95% CI 0.98-1.14, p=0.12) and random-effects model, 1.10 (0.93-1.30, p=0.28) in overall and in the subgroup analysis by ethnicity. Similar results were also obtained for all genetic models in the stratified analyses by new definition of drug-resistance by ILAE and ethnicity subgroups. There was no publication bias.
CONCLUSION
We failed to show an association between the ABCB1 C3435T polymorphism and the risk of drug-resistance suggesting a revision in contribution of this polymorphism in the multi-drug transporters hypothesis of pharmacoresistance to AEDs in epilepsy.
Topics: ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily B, Member 1; Anticonvulsants; Data Interpretation, Statistical; Drug Resistance; Epilepsy; Gene Frequency; Genetic Variation; Genotype; Humans; Polymorphism, Genetic; Research Design; Risk Assessment
PubMed: 20605481
DOI: 10.1016/j.seizure.2010.05.004 -
Current Cancer Drug Targets May 2009A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship... (Review)
Review
A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship between cisplatin and paclitaxel. Here we systematically review genetically modified cell lines in which the inverse cisplatin/paclitaxel resistance phenotype has resulted. This will form a short list of genes which may play a role in the mechanism of the inverse resistance relationship as well as act as potential markers for monitoring the development of resistance in the clinical treatment of cancer. The literature search revealed 91 genetically modified cell lines which report toxicity or viability/apoptosis data for cisplatin and paclitaxel relative to their parental cell lines. This resulted in 26 genes being associated with the inverse cisplatin/paclitaxel phenotype. The gene with the highest number of genetically modified cell lines associated with the inverse resistance relationship was BRCA1 and this gene is discussed in detail with reference to chemotherapy response in cell lines and in the clinical treatment of breast, ovarian and lung cancer. Other genes associated with the inverse resistance phenotype included dihydrodiol dehydrogenase (DDH) and P-glycoprotein. Genes which caused cross resistance or cross sensitivity between cisplatin and paclitaxel were also examined, the majority of these genes were apoptosis associated genes which may be useful for predicting cross resistance. We propose that BRCA1 should be the first of a panel of cellular markers to predict the inverse cisplatin/paclitaxel resistance phenotype.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Antineoplastic Agents; BRCA1 Protein; Cell Line, Tumor; Cisplatin; Female; Genes, BRCA1; Humans; Neoplasms; Oxidoreductases; Paclitaxel; Phenotype; Treatment Outcome
PubMed: 19442054
DOI: 10.2174/156800909788166592 -
Journal of Nuclear Medicine : Official... Mar 2009Multidrug resistance (MDR) is a major problem in lung cancer. (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been demonstrated to be a noninvasive marker for the... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
Multidrug resistance (MDR) is a major problem in lung cancer. (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been demonstrated to be a noninvasive marker for the diagnosis of MDR-related P glycoprotein and MDR-associated protein expression in various solid tumors. Studies have shown that (99m)Tc-MIBI could play a significant role in the management of lung cancer; for example, it could be used in the selection of patients for chemotherapy or radiotherapy or in combined protocols before the start of treatment. Accurate selection of chemosensitive patients with (99m)Tc-MIBI would result not only in effective treatment of patients but also in significant cost savings for health care providers. There is increasing pressure on health care providers to consider costs in medical decision making, particularly in the last decade, as several economic evaluations have appeared in the medical literature. The aims of this study were to undertake a systematic review of the performance of (99m)Tc-MIBI imaging in the assessment of treatment resistance in lung cancer and to use the findings of the review in a decision tree analysis of the potential cost-effectiveness of (99m)Tc-MIBI imaging in selecting lung cancer patients for chemotherapy.
METHODS
This study included a systematic review of the literature and a meta-analysis together with a cost-effectiveness analysis of studies with a decision tree analysis model.
RESULTS
Analysis of the studies revealed that the overall sensitivity of (99m)Tc-MIBI in identifying responders to chemotherapy was 94%, the specificity was 90%, and the accuracy was 92%. The sensitivity analysis revealed an incremental cost-effectiveness ratio of greater than pound30,000 ( approximately $42,900) for the strategy of treating all patients to recover the small loss of life expectancy (7.5 d) associated with the use of (99m)Tc-MIBI to preselect patients for chemotherapy.
CONCLUSION
(99m)Tc-MIBI SPECT can accurately predict which patients with lung cancer will respond to chemotherapy. The use of (99m)Tc-MIBI to preselect patients for chemotherapy has the potential to yield significant cost savings in the health care system without a significant loss of life expectancy for patients.
Topics: Cost-Benefit Analysis; Decision Trees; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon; Treatment Outcome
PubMed: 19223414
DOI: 10.2967/jnumed.108.055988