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Pharmaceutical Research Sep 2020The involvement of the intestinally expressed xenobiotic transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) have been implicated in apixaban...
PURPOSE
The involvement of the intestinally expressed xenobiotic transporters P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) have been implicated in apixaban disposition based on in vitro studies. Recommendations against co-administration of apixaban with inhibitors of these efflux transporters can be found throughout the literature as well as in the apixaban FDA label. However, the clinical relevance of such findings is questionable due to the high permeability and high solubility characteristics of apixaban.
METHODS
Using recently published methodologies to discern metabolic- from transporter- mediated drug-drug interactions, a critical evaluation of all published apixaban drug-drug interaction studies was conducted to investigate the purported clinical significance of efflux transporters in apixaban disposition.
RESULTS
Rational examination of these clinical studies using basic pharmacokinetic theory does not support the clinical significance of intestinal efflux transporters in apixaban disposition. Further, there is little evidence that efflux transporters are clinically significant determinants of systemic clearance.
CONCLUSIONS
Inhibition or induction of intestinal CYP3A4 can account for exposure changes of apixaban in all clinically significant drug-drug interactions, and lack of intestinal CYP3A4 inhibition can explain all studies with no exposure changes, regardless of the potential for these perpetrators to inhibit intestinal or systemic efflux transporters.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Biological Transport; Cytochrome P-450 CYP3A; Drug Interactions; Humans; Intestinal Absorption; Neoplasm Proteins; Pyrazoles; Pyridones
PubMed: 32996065
DOI: 10.1007/s11095-020-02927-4 -
British Journal of Clinical Pharmacology Oct 2002The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible. (Review)
Review
AIMS
The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible.
METHODS
A systematic review of all the available evidence, including worldwide published literature and spontaneous case reports provided by healthcare professionals and regulatory authorities within Europe has been undertaken.
RESULTS
A number of clinically significant interactions have been identified with prescribed medicines including warfarin, phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and oral contraceptives resulting in a decrease in concentration or effect of the medicines. These interactions are probably due to the induction of cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein by constituent(s) in SJW. The degree of induction is unpredictable due to factors such as the variable quality and quantity of constituent(s) in SJW preparations. In addition, possible pharmacodynamic interactions with selective serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such as triptans used to treat migraine were identified. These interactions are associated with an increased risk of adverse reactions.
CONCLUSIONS
In Sweden and the UK the potential risks to patients were judged to be significant and therefore information about the interactions was provided to health care professionals and patients. The product information of the licensed medicines involved has been amended to reflect these newly identified interactions and SJW preparations have been voluntarily labelled with appropriate warnings.
Topics: Contraceptives, Oral; Cyclosporine; Digoxin; Drug Interactions; HIV Protease Inhibitors; Herb-Drug Interactions; Humans; Hypericum; Plant Extracts; Selective Serotonin Reuptake Inhibitors; Theophylline; Warfarin
PubMed: 12392581
DOI: 10.1046/j.1365-2125.2002.01683.x -
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 -
European Journal of Clinical... Jun 2024Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of... (Review)
Review
OBJECTIVES
Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of linezolid are often overlooked. This manuscript aims to review the medications that affect the pharmacokinetics of linezolid.
METHODS
In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, Embase, and Cochrane Library for publications from database establishment to November 3, 2023, using the search terms: "Linezolid" and "interaction," or "interact," or "drug-drug interaction," or "co-treatment," or "cotreatment," or "combined," or "combination."
RESULTS
A total of 24 articles were included. Among the reported medication interactions, rifampicin, levothyroxine, venlafaxine, and phenobarbital could reduce the concentration of linezolid; clarithromycin, digoxin, cyclosporine, proton pump inhibitors, and amiodarone could increase the concentration of linezolid, while aztreonam, phenylpropanolamine, dextromethorphan, antioxidant vitamins, and magnesium-containing antacids had no significant effects on linezolid pharmacokinetics. The ratio of mean (ROM) of linezolid AUC in co-treatment with rifampicin to monotherapy was 0.67 (95%CI 0.58-0.77) and 0.63 (95%CI 0.43-0.91), respectively, in 2 studies, and co-treatment with 500 mg clarithromycin to monotherapy was 1.81 (95%CI 1.49-2.13).
CONCLUSIONS
This systematic review found that numerous drugs have an impact on the pharmacokinetics of linezolid, and the purported main mechanism may be that linezolid is the substrate of P-glycoprotein. In clinical practice, it is prudent to pay attention to the changes in linezolid pharmacokinetics caused by interactions. Conducting therapeutic drug monitoring (TDM) is beneficial to improve efficacy and reduce adverse reactions of linezolid.
Topics: Drug Interactions; Linezolid; Humans; Anti-Bacterial Agents
PubMed: 38421436
DOI: 10.1007/s00228-024-03652-2 -
Expert Opinion on Drug Safety May 2013In recent years, the number of oral antitumoral agents has considerably increased. Oral administration increases the risk of interactions, because most oral anticancer... (Review)
Review
INTRODUCTION
In recent years, the number of oral antitumoral agents has considerably increased. Oral administration increases the risk of interactions, because most oral anticancer drugs are taken on a daily basis. Interactions can increase exposure to antitumoral agents or cause treatment failure. Many antitumoral drugs undergo enzymatic metabolism by cytochrome P450. As some act as inducers or inhibitors of one or more isoenzymes, they can lead to decreases or increases in plasma concentrations of concomitant drugs. Hence, cytostatic drugs can act not only as victims but also as perpetrators. P-glycoprotein, an efflux transporter, can also be involved in pharmacokinetic interactions.
AREAS COVERED
A Medline search was performed to summarize the available evidence of the most clinically relevant interactions between oral chemotherapy agents and other drugs. The search covered the period from 1966 until August 2012 for each antitumoral drug using the medical subject headings 'Drug Interactions' OR 'Pharmacokinetics'. While the present review is not exhaustive, it aims to increase clinicians' awareness of potential drug-drug interactions.
EXPERT OPINION
As cancer patients are often polymedicated and treated by different physicians, the risk of drug interactions between antitumoral agents and other medications is high. More clinical interaction studies are encouraged to ensure appropriate antineoplastic pharmacokinetics in clinical practice.
Topics: Administration, Oral; Antineoplastic Agents; Cytochrome P-450 Enzyme System; Drug Interactions; Humans
PubMed: 23586848
DOI: 10.1517/14740338.2013.784268 -
The Journal of International Medical... Jul 2019A relationship between polymorphisms rs1128503 and rs1045642 in the multidrug resistance 1 gene () and susceptibility to hepatocellular carcinoma (HCC) has been reported... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
A relationship between polymorphisms rs1128503 and rs1045642 in the multidrug resistance 1 gene () and susceptibility to hepatocellular carcinoma (HCC) has been reported but is inconclusive. This study was performed to explore the significance of polymorphisms rs1128503 and rs1045642 in screening and diagnosis of HCC.
METHODS
Studies of association analyses between gene polymorphisms rs1128503 and rs1045642 and HCC were selected from three foreign language databases (PubMed, Cochrane, and Embase) and three Chinese databases (Wanfang, China National Knowledge Infrastructure, and China Knowledge Network) and subjected to meta-analysis.
RESULTS
We found no significant relationship between the rs1128503 polymorphism and susceptibility to HCC in 4 cohorts and no significant relationship between the rs1045642 polymorphism and susceptibility to HCC in 3 cohorts.
CONCLUSIONS
There was no relationship between polymorphisms rs1128503 or rs1045642 of the gene and susceptibility to HCC.
Topics: ATP Binding Cassette Transporter, Subfamily B; Carcinoma, Hepatocellular; Genetic Predisposition to Disease; Humans; Liver Neoplasms; Polymorphism, Single Nucleotide; Prognosis
PubMed: 31234681
DOI: 10.1177/0300060519855869 -
Journal of Ethnopharmacology Mar 2021Bisbenzylisoquinoline (BBIQ) alkaloids are generally present in plants of Berberidaceae, Monimiaceae and Ranunculaceae families in tropical and subtropical regions. Some...
RELEVANCE
Bisbenzylisoquinoline (BBIQ) alkaloids are generally present in plants of Berberidaceae, Monimiaceae and Ranunculaceae families in tropical and subtropical regions. Some species of these families are used in traditional Chinese medicine, with the effects of clearing away heat and detoxification, promoting dampness and defecation, and eliminating sores and swelling. This article offers essential data focusing on 13 representative BBIQ compounds, which are mainly extracted from five plants. The respective botany, traditional uses, phytochemistry, pharmacokinetics, and toxicity are summarized comprehensively. In addition, the ADME prediction of the 13 BBIQ alkaloids is compared and analyzed with the data obtained.
MATERIALS AND METHODS
We have conducted a systematic review of the botanical characteristics, traditional uses, phytochemistry, pharmacokinetics and toxicity of BBIQ alkaloids based on literatures collected from PubMed, Web of Science and Elsevier during 1999-2020. ACD/Percepta software was utilized to predict the pharmacokinetic parameters of BBIQ alkaloids and their affinity with enzymes and transporters.
RESULTS
Botany, traditional uses, phytochemistry, pharmacokinetic and toxicity of 13 alkaloids, namely, tetrandrine, dauricine, curine, trilobine, isotrilobine, cepharanthine, daurisoline, thalicarpine, thalidasine, isotetrandrine, liensinine, neferine and isoliensinine, have been summarized in this paper. It can't be denied that these alkaloids are important material basis of pharmacological effects of family Menispermaceae and others, and for traditional and local uses which has been basically reproduced in the current studies. The 13 BBIQ alkaloids in this paper showed strong affinity and inhibitory effect on P-glycoprotein (P-gp), with poor oral absorption and potent binding ability with plasma protein. BBIQ alkaloids represented by tetrandrine play a key role in regulating P-gp or reversing multidrug resistance (MDR) in a variety of tumors. The irrationality of their usage could pose a risk of poisoning in vivo, including renal and liver toxicity, which are related to the formation of quinone methide during metabolism.
CONCLUSION
Although there is no further clinical evaluation of BBIQ alkaloids as MDR reversal agents, their effects on P-gp should not be ignored. Considering their diverse distribution, pharmacokinetic characteristics and toxicity reported during clinical therapy, the quality standards in different plant species and the drug dosage remain unresolved problems.
Topics: Alkaloids; Animals; Benzylisoquinolines; Drugs, Chinese Herbal; Ethnobotany; Ethnopharmacology; Humans; Medicine, Chinese Traditional; Phytochemicals; Plants, Medicinal
PubMed: 33166629
DOI: 10.1016/j.jep.2020.113566 -
Clinical Drug Investigation Nov 2020Direct oral anticoagulants (DOACs), as substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, are susceptible to drug-drug interactions (DDIs). Hepatitis C...
BACKGROUND
Direct oral anticoagulants (DOACs), as substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, are susceptible to drug-drug interactions (DDIs). Hepatitis C direct-acting antiviral agents (DAAs), via P-glycoprotein or CYP3A4 inhibition, may increase DOAC exposure with relevant bleeding risk. We performed a systematic review on DDIs between DOACs and DAAs.
METHODS
Two reviewers independently identified studies through electronic databases, until 7 July 2020, supplementing the search by reviewing conference abstracts and the ClinicalTrials.gov website.
RESULTS
Of 1386 identified references, four articles were finally included after applying the exclusion criteria. Three phase I clinical studies in healthy volunteers assessed interactions between dabigatran and glecaprevir/pibrentasvir, odalasvir/simeprevir, or sofosbuvir/velpatasvir/voxilaprevir, showing an increase in the dabigatran area under the concentration-time curve (AUC) by 138%, 103%, and 161%, respectively.
CONCLUSIONS
DOACs and DAAs are under-investigated for DDI risk. Real-world studies are needed to assess the clinical relevance of the pharmacokinetic interactions with dabigatran and describe the actual spectrum of possible DDIs between DAAs and other DOACs.
Topics: Anticoagulants; Antiviral Agents; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Hepatitis C; Humans
PubMed: 32809123
DOI: 10.1007/s40261-020-00962-y -
Cells Mar 2024Chemoresistance is a challenge in cancer treatment, limiting the effectiveness of chemotherapy. Mushroom extracts have shown potential as treatments for cancer... (Review)
Review
Chemoresistance is a challenge in cancer treatment, limiting the effectiveness of chemotherapy. Mushroom extracts have shown potential as treatments for cancer therapies, offering a possible solution to overcome chemoresistance. This systematic review aimed to explore the role of mushroom extracts in enhancing chemotherapy and reversing chemoresistance in cancer cells. We searched the PubMed, Web of Science and Scopus databases, following the PRISMA guidelines, and registered on PROSPERO. The extracts acted by inhibiting the proliferation of cancer cells, as well as enhancing the effect of chemotherapy. The mechanisms by which they acted included regulating anti-apoptotic proteins, inhibiting the JAK2/STAT3 pathway, inhibiting the ERK1/2 pathway, modulating microRNAs and regulating p-glycoprotein. These results highlight the potential of mushroom extracts to modulate multiple mechanisms in order to improve the efficacy of chemotherapy. This work sheds light on the use of mushroom extracts as an aid to chemotherapy to combat chemoresistance. Although studies are limited, the diversity of mushrooms and their bioactive compounds show promising results for innovative strategies to treat cancer more effectively. It is crucial to carry out further studies to better understand the therapeutic potential of mushroom extracts to improve the efficacy of chemotherapy in cancer cells.
Topics: Agaricales; Neoplasms; MicroRNAs; MAP Kinase Signaling System
PubMed: 38534354
DOI: 10.3390/cells13060510 -
International Journal of Nanomedicine 2019The poor pharmacokinetic characteristics of most anticancer drugs have limited their clinical effectiveness. The application of nanoparticles as a novel drug delivery...
The poor pharmacokinetic characteristics of most anticancer drugs have limited their clinical effectiveness. The application of nanoparticles as a novel drug delivery system has provided opportunities to tackle the current challenges facing conventional drug delivery systems such as poor pharmacokinetics, lack of specificity to tumor cells, multidrug resistance, and toxicity. This systematic review aims to examine the application of pharmacokinetic studies of nanoparticles loaded in conventional drugs and herb-derived compounds for cancer therapy. The pharmacokinetic parameters of several herbal medicines and chemotherapeutic drugs loaded into nanoparticles were reported. This included area under the curve (AUC) of plasma concentration-time profile, maximum plasma concentration (C), time to maximum plasma concentration (T), volume of distribution (V or V), elimination half-life (t), and clearance (CL). The systematic review was conducted using information available in the PubMed and Science Direct databases up to February 2019. The search terms employed were: pharmacokinetics, pharmacokinetic study, nanoparticles, anticancer, traditional medicine, herbal medicine, herb-derived compounds, natural products, and chemotherapy. Overall, nanoparticle carriers not only significantly improved pharmacokinetics but also further enhanced permeability, solubility, stability, specificity, and selectivity of the carried anticancer drugs/herb-derived compounds to target tumor cells. Additionally, they also limited hepatic first-pass metabolism and P-glycoprotein (P-gp) efflux of the carried anticancer drugs/herb-derived compounds. Based on this systematic review, polymeric nanoparticles were the most commonly used nanocarrier to improve the pharmacokinetic parameters. The use of nanoparticles as a novel drug delivery system has the potential to improve both pharmacokinetics and cytotoxicity activity of the loaded drugs/herb-derived compounds for cancer therapy.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Humans; Nanoparticles; Neoplasms; Plants, Medicinal
PubMed: 31632004
DOI: 10.2147/IJN.S213229