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Journal of Managed Care & Specialty... Mar 2018Generic drugs are bioequivalent and cost-effective alternatives to brand drugs. In 2014, $254 billion was saved because of the use of generic drugs in the United States. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Generic drugs are bioequivalent and cost-effective alternatives to brand drugs. In 2014, $254 billion was saved because of the use of generic drugs in the United States.
OBJECTIVE
To critically assess evidence on the association between patient characteristics and generic drug use in order to inform the development of educational outreach for improving generic drug use among patients.
METHODS
We systematically searched the literature between January 2005 and December 2016 using PubMed, Web of Science, Ovid MEDLINE, Google Scholar, and EBSCO IPA-MEDLINE for potentially relevant studies. The titles and abstracts of identified articles were assessed independently by 2 reviewers. Titles and abstracts that were not written in English, were published before 2005, were not empirical, did not contain sociodemographic data, or were not policy or methodologically relevant to generic drug use were excluded. Data were pooled in a meta-analysis using the RStudio software to assess the association of patient-related factors with generic drug use.
RESULTS
Our searches resulted in 11 articles on patient-level factors, and 6 of these articles had sufficient information to conduct meta-analyses in the domains of patients' gender, age, race/ethnicity, and income. Quantitative analysis indicated that no differences in generic drug use existed between subgroups of patients defined by gender, age, or race/ethnicity. However, patients with lower income (i.e., < 200% federal poverty level [FPL]) were more likely to use generic drugs than those with higher income (≥ 200% FPL; pooled OR = 1.32, 95% CI = 1.15-1.52). Heterogeneity was high (I > 75%) for all analyses but income.
CONCLUSIONS
Patients with lower income were more likely to use generic drugs, whereas evidence was heterogeneous regarding an association between generic drug use and gender, age, or race/ethnicity. Educational outreach targeting patients with higher incomes to understand their perspectives in generic drugs may help improve generic drug use within that population.
DISCLOSURES
Funding for this study was made possible, in part, by the U.S. Food and Drug Administration through grant U01FD005486. Hansen has provided expert testimony for Daiichi Sankyo. No other authors have declared a potential conflict of interest. Views expressed in written materials or publications and by speakers do not necessarily reflect the official policies of the U.S. Department of Health and Human Services, nor does any mention of trade names, commercial practices, or organization imply endorsement by the U.S. government. Study concept and design were contributed by Howard, Harris, Kiptanui, Hansen, and Qian. Frank, Mishuk, Howard, Harris, and Kiptanui collected the data, and data interpretation was performed by Mishuk and Hansen, along with Qian, Harris, and Kiptanui. The manuscript was written and revised primarily by Mishuk, along with Qian and Hansen.
Topics: Cost-Benefit Analysis; Drugs, Generic; Humans; Social Class; Therapeutic Equivalency
PubMed: 29485953
DOI: 10.18553/jmcp.2018.24.3.252 -
International Journal of Clinical... Aug 2015This study was conducted to provide a narrative overview of interactions between smoking and drug effectiveness/ pharmacokinetics. Database searches were performed to... (Review)
Review
This study was conducted to provide a narrative overview of interactions between smoking and drug effectiveness/ pharmacokinetics. Database searches were performed to identify review articles published prior to March 10, 2013. Eligible articles reporting altered pharmacokinetic profiles, drug response, or adverse drug effects due to drug-smoking interactions were selected. Information on mechanism of action and clinical effects from the selected articles (n = 83) were summarized by therapeutic drug class. For cardiovascular drugs, smoking effects were variable. Smoking reduced aspirin response but increased clopidogrel response by increasing active metabolites. Warfarin, which has a narrow therapeutic range, required dosage adjustment in smokers due to its rapid clearance. Smoking is a risk factor for respiratory disease, leading to a lower response to corticosteroid and requiring increased doses or additional drugs. Higher doses of theophylline and some antipsychotics, which are mainly metabolized by CYP1A2, are required to reach an optimal plasma concentration in smokers. Smoking is also a risk factor for cancer, especially for lung cancer. Erlotinib or gefitinib are epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for lung cancer and showed lower anticancer effects in smokers. This summary of the interactions between smoking and drug pharmacological properties will aid healthcare professionals in providing patients with appropriate drug therapies, and emphasizes the need for considering smoking status as a patient factor in the clinical setting.
Topics: Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Patient Safety; Patient Selection; Pharmaceutical Preparations; Pharmacokinetics; Risk Assessment; Risk Factors; Smoking
PubMed: 26104035
DOI: 10.5414/CP202260 -
British Journal of Clinical Pharmacology Jun 2018Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in...
AIMS
Saliva, as a matrix, offers many benefits over blood in therapeutic drug monitoring (TDM), in particular for infantile TDM. However, the accuracy of salivary TDM in infants remains an area of debate. This review explored the accuracy, applicability and advantages of using saliva TDM in infants and neonates.
METHODS
Databases were searched up to and including September 2016. Studies were included based on PICO as follows: P: infants and neonates being treated with any medication, I: salivary TDM vs. C: traditional methods and O: accuracy, advantages/disadvantages and applicability to practice. Compounds were assessed by their physicochemical and pharmacokinetic properties, as well as published quantitative saliva monitoring data.
RESULTS
Twenty-four studies and their respective 13 compounds were investigated. Four neutral and two acidic compounds, oxcarbazepine, primidone, fluconazole, busulfan, theophylline and phenytoin displayed excellent/very good correlation between blood plasma and saliva. Lamotrigine was the only basic compound to show excellent correlation with morphine exhibiting no correlation between saliva and blood plasma. Any compound with an acid dissociation constant (pKa) within physiological range (pH 6-8) gave a more varied response.
CONCLUSION
There is significant potential for infantile saliva testing and in particular for neutral and weakly acidic compounds. Of the properties investigated, pKa was the most influential with both logP and protein binding having little effect on this correlation. To conclude, any compound with a pKa within physiological range (pH 6-8) should be considered with extra care, with the extraction and analysis method examined and optimized on a case-by-case basis.
Topics: Age Factors; Drug Monitoring; Humans; Infant; Infant, Newborn; Pharmaceutical Preparations; Pharmacokinetics; Predictive Value of Tests; Reproducibility of Results; Saliva
PubMed: 29442362
DOI: 10.1111/bcp.13553 -
High Altitude Medicine & Biology Jun 2018Bailey, Damian Miles, Benjamin S. Stacey, and Mark Gumbleton. A systematic review and meta-analysis reveals altered drug pharmacokinetics in humans during acute exposure... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-Analysis Reveals Altered Drug Pharmacokinetics in Humans During Acute Exposure to Terrestrial High Altitude-Clinical Justification for Dose Adjustment?
UNLABELLED
Bailey, Damian Miles, Benjamin S. Stacey, and Mark Gumbleton. A systematic review and meta-analysis reveals altered drug pharmacokinetics in humans during acute exposure to terrestrial high altitude-clinical justification for dose adjustment? High Alt Med Biol. 19:141-148, 2018.
OBJECTIVE
While physiological responses during acute ascent to terrestrial high altitude (HA) have the potential to alter the pharmacokinetics (PKs) that define absorption and disposition of medicinal drugs, there have been no systematic reviews and meta-analyses performed to date.
METHODS
We conducted a systematic literature search in June 2017 using NCBI PubMed, EMBASE, Web of Science, and Ovid MEDLINE databases to identify relevant observational studies. Studies were deemed eligible based on the following criteria: (1) participants: healthy, nonacclimatized male or female lowlanders (born and bred at sea level) and (2) environment: exposure to low altitude (LA, ≤600 m), followed by terrestrial high altitude (HA, ≤24 hours to ≥2500 m), the time course specifically selected to avoid interpretive complications associated with erythrocytosis. All PK parameters were standardized to be in the same units and the weighted standardized mean difference (SMD) calculated using a combination of fixed and random effects models with heterogeneity evaluated using χ and I statistics.
RESULTS
Of 20,840 studies reviewed, 6 prospective cohort studies (n = 75) qualified for inclusion, with participants exposed to a mean altitude of 4025 (mean) ± 380 (SD) m. We observed increases for absorption half-life (SMD: 0.40, 95% CI: 0.01-0.80, p = 0.04], elimination half-life (SMD: 0.89, 95% CI: 0.30-1.48, p = 0.003), and erythrocyte binding (SMD: 0.52, 95% CI: 0.16-0.88, p = 0.004) and reduction in clearance (SMD: -0.56, 95% CI: -1.13 to 0.00, p = 0.05).
CONCLUSIONS
Collectively, these findings reveal impairments in both oral absorption and corresponding clearance of the, although limited, sample of drugs at HA that may potentially require closer patient monitoring and dose adjustments to maintain therapeutic efficacy and avoid incidental toxicity.
Topics: Absorption, Physiological; Acclimatization; Adult; Altitude; Erythrocytes; Female; Half-Life; Humans; Male; Metabolic Clearance Rate; Middle Aged; Pharmacokinetics; Prospective Studies
PubMed: 29620950
DOI: 10.1089/ham.2017.0121 -
Human & Experimental Toxicology Sep 2011Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as... (Review)
Review
Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.
Topics: Animals; Carbamates; Carbohydrate Metabolism; Databases, Bibliographic; Humans; Hydrocarbons, Chlorinated; Lipid Metabolism; Metabolic Diseases; Organophosphates; Oxidative Stress; Pesticides; Proteins
PubMed: 21071550
DOI: 10.1177/0960327110388959 -
Medicine Feb 2021The goals of improving quality of life and increasing longevity are receiving growing amounts of attention. Body weight and lipid metabolism are closely related to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The goals of improving quality of life and increasing longevity are receiving growing amounts of attention. Body weight and lipid metabolism are closely related to various complications of diabetes. The aim of this study was to rank SGLT inhibitors according to their efficacy with regard to weight and evaluate the effect of SGLT inhibitors on lipid metabolism at 24 weeks of treatment.
METHODS
The Web of Science, PubMed, Cochrane Library, Embase, and Clinical Trials databases were electronically searched to collect randomized controlled trials involving patients with type 2 diabetes mellitus through June 2020. Two researchers independently screened and evaluated the selected studies and extracted the outcome indexes. ADDIS 1.16.5 and STATA 16 software were used to perform the network meta-analysis and draw the plots.
RESULTS
Ultimately, 36 studies were selected and included in this study. We found that all SGLT inhibitors were effective at reducing weight; canagliflozin was the most effective. SGLT inhibitors and placebo were not associated with significantly different serum cholesterol levels. SGLT inhibitors lowered serum triglyceride levels and increased serum high-density and low-density lipoprotein cholesterol levels. SGLT inhibitors also reduced the level of alanine aminotransferase.
CONCLUSIONS
SGLT inhibitors can bring about weight loss in patients with T2DM and can also improve lipid metabolism. Therefore, patients with hyperlipidemia who have been unsuccessful at losing weight should consider taking SGLT inhibitors. In addition, SGLT inhibitors are hepatoprotective and appear to be safe for patients with mild to moderate liver dysfunction.
TRIAL REGISTRATION
CRD42020198516.
Topics: Body Weight; Diabetes Mellitus, Type 2; Humans; Lipid Metabolism; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 33578559
DOI: 10.1097/MD.0000000000024593 -
Wiley Interdisciplinary Reviews. RNA Nov 2021In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding... (Review)
Review
In the last decade, an intriguing new paradigm of regulation has emerged in which some transcripts longer than 200 nucleotides and no coding potential, long noncoding RNA (lncRNAs), exhibit the capability to control posttranslational modifications of nonhistone proteins in both invertebrates and vertebrates. The extent of such a regulation is still largely unknown. We performed a systematic review to identify and evaluate the potential impact of lncRNA-dependent methylation of nonhistone proteins. Collectively, these lncRNAs primarily act as scaffolds upon which methyltransferases (MTases) and targets are brought in proximity. In this manner, the N-MTase activity of EZH2, protein arginine-MTase 1/4/5, and SMYD2 is exploited to modulate the stability or the compartmentalization of several nonhistone proteins with roles in cell signaling, gene expression, and RNA processing. Moreover, these lncRNAs can indirectly affect the methylation of nonhistone proteins by transcriptional or posttranscriptional regulation of MTases. Strikingly, the lncRNAs/MTases/nonhistone proteins networking seem to be relevant to carcinogenesis and neurological disorders. This article is categorized under: Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs.
Topics: Animals; Gene Expression Regulation; Methylation; Protein Processing, Post-Translational; RNA Processing, Post-Transcriptional; RNA, Long Noncoding
PubMed: 33913612
DOI: 10.1002/wrna.1661 -
The Journal of Trauma and Acute Care... Jan 2016The hypermetabolic state after severe burns is a major problem that can lead to several pathophysiologic changes and produce multiple sequelae. Adrenergic blockade has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The hypermetabolic state after severe burns is a major problem that can lead to several pathophysiologic changes and produce multiple sequelae. Adrenergic blockade has been widely used to reverse these changes and improve outcomes in burned patients but has not been rigorously evaluated. The aim of this systematic review was to investigate the efficacy and safety of the use of adrenergic blockade after burn injury.
METHODS
The databases MEDLINE via OVID, PubMed, EMBASE, CINAHL, Cochrane Library, and Web of Science were searched from inception to December 2014 with search terms including burns and beta-blockers with appropriate synonyms. Articles were restricted to those published in English, French, or Spanish. Randomized controlled trials, nonrandomized controlled trials, and systematic reviews were screened. After an independent screening and full-text review, 10 articles were selected, and an appraisal of risk of bias was performed.
RESULTS
From 182 articles screened, 9 randomized controlled trials and 1 nonrandomized controlled trial met the inclusion criteria. Pooled analyses were performed to calculate effect sizes and 95% confidence intervals (CIs). There was a positive effect favoring propranolol use that significantly decreased resting energy expenditure (g = -0.64; 95% CI, -0.8 to -0.5; p < 0.001) and trunk fat (g = -0.3; 95% CI, -0.4 to -0.1; p < 0.001) as well as improved peripheral lean mass (g = 0.45; 95% CI, 0.3-0.6; p < 0.001) and insulin resistance (g = -1.35; 95% CI, -2.0 to -0.6; p < 0.001). Occurrence of adverse events was not significantly different between the treated patients the and controls.
CONCLUSION
Limited evidence suggests beneficial effects of propranolol after burn injury, and its use seems safe. However, further trials on adult population with a broader range of outcome measures are warranted.
LEVEL OF EVIDENCE
Systematic review and meta-analysis, level III.
Topics: Adrenergic beta-Antagonists; Burns; Energy Metabolism; Humans; Patient Safety; Propranolol
PubMed: 26517779
DOI: 10.1097/TA.0000000000000887 -
European Journal of Medicinal Chemistry Dec 2023Proteolysis-targeting chimeras (PROTACs) have been an area of intensive research with the potential to extend drug space not target to traditional molecules. In the last... (Review)
Review
Proteolysis-targeting chimeras (PROTACs) have been an area of intensive research with the potential to extend drug space not target to traditional molecules. In the last half decade, we have witnessed several PROTACs initiated phase I/II/III clinical trials, which inspired us a lot. However, the structure of PROTACs beyond "rule of 5" resulted in developing PROTACs with acceptable oral pharmacokinetic (PK) properties remain one of the biggest bottleneck tasks. Many reports have demonstrated that it is possible to access orally bioavailable PROTACs through rational ligand and linker modifications. In this review, we systematically reviewed and highlighted the most recent advances in orally bioavailable PROTACs development, especially focused on the medicinal chemistry campaign of discovery process and in vivo oral PK properties. Moreover, the constructive strategies for developing oral PROTACs were proposed comprehensively. Collectively, we believe that the strategies summarized here may provide references for further development of oral PROTACs.
Topics: Proteolysis Targeting Chimera; Chemistry, Pharmaceutical; Proteolysis; Ubiquitin-Protein Ligases
PubMed: 37708797
DOI: 10.1016/j.ejmech.2023.115793 -
Epilepsia Open Apr 2024Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this... (Review)
Review
Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this systematic review is to provide practical and useful information regarding various aspects of the interactions between ASMs and foods and drinks. MEDLINE and ScienceDirect, from the inception to July 15, 2023, were searched for related publications. In both electronic databases, the following search strategy was applied, and the following keywords were used (in title/abstract): "food OR drink" AND "antiepileptic OR antiseizure." The primary search yielded 738 studies. After implementing our inclusion and exclusion criteria, we could identify 19 studies on the issue of interest for our endeavor. Four studies were identified in the recheck process and not by the primary search. All studies provided low level of evidence. Interactions between foods and ASMs are a common phenomenon. Many factors may play a role for such an interaction to come to play; these include drug properties, administration route, and administration schedule, among others. Drugs-foods (-drinks) interactions may change the drug exposure or plasma levels of drugs (e.g., grapefruit juice increases carbamazepine concentrations and the bioavailability of cannabidiol is increased 4-5 folds with concomitant intake of fat-rich food); this may require dosage adjustments. Interactions between ASMs and foods and drinks may be important. This should be taken seriously into consideration when consulting patients and their caregivers about ASMs. Future well-designed investigations should explore the specific interactions between foods (and drinks) and ASMs to clarify whether they are clinically important. PLAIN LANGUAGE SUMMARY: Interactions between antiseizure medications and foods and drinks may be important. This should be taken into consideration in patients with epilepsy.
Topics: Humans; Anticonvulsants; Biological Availability; Benzodiazepines; Food; Epilepsy
PubMed: 38345419
DOI: 10.1002/epi4.12918