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Pharmacotherapy Apr 2021Cannabidiol (CBD), a non-psychotropic phytocannabinoid from the Cannabis plant, is increasingly being pursued as a treatment for differing ailments. The bioavailability...
Cannabidiol (CBD), a non-psychotropic phytocannabinoid from the Cannabis plant, is increasingly being pursued as a treatment for differing ailments. The bioavailability and pharmacokinetics of CBD are not well understood, and proper dosing schemes have not been adequately developed for its clinical use. CBD is a lipophilic molecule and exhibits low water solubility, so its formulation expectedly impacts its gastrointestinal absorption and subsequent blood plasma concentrations. In this review article, the food effects on CBD pharmacokinetics were analyzed. Clinical trials focusing on the performance of Epidiolex, the FDA-approved CBD formulation, were found in several databases and systematically analyzed in terms of administration method, dosing schedules, and patient characteristics. 44 data sets from clinical trials were found to be useful in the quantitative analysis. Following the normalization of all the pharmacokinetic data sets by dose and patient weight, CBD exhibited a much greater bioavailability in fed patients. For Epidiolex, administration in the fed state led to lower interindividual variability and more predictable pharmacokinetics. Considering all the different oral formulations of CBD, further analysis points to the main excipient of oral CBD formulations (refined sesame seed oil) as a major contributor to the dose-dependent variations in CBD pharmacokinetics, especially affecting the fasted state. We discuss the implications of these results on the downstream pharmacodynamics of endocannabinoid receptor modulation and its broad physiological implications.
Topics: Biological Availability; Cannabidiol; Clinical Trials as Topic; Food; Humans
PubMed: 33583102
DOI: 10.1002/phar.2512 -
Influenza and Other Respiratory Viruses Nov 2021Standard-dose seasonal influenza vaccines often produce modest immunogenic responses in adults ≥65 years old. MF59 is intended to elicit a greater magnitude and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Standard-dose seasonal influenza vaccines often produce modest immunogenic responses in adults ≥65 years old. MF59 is intended to elicit a greater magnitude and increased breadth of immune response.
OBJECTIVE
To determine the effectiveness of seasonal MF59-adjuvanted trivalent/quadrivalent influenza vaccine (aTIV/aQIV) relative to no vaccination or vaccination with standard or high-dose egg-based influenza vaccines among people ≥65 years old.
METHODS
Cochrane methodological standards and PRISMA-P guidelines were followed. Real-world evidence from non-interventional studies published in peer-reviewed journals and gray literature from 1997 through to July 15, 2020, including cluster-randomized trials, were eligible. Two reviewers independently extracted data; risk of bias was assessed using the ROBINS-I tool.
RESULTS
Twenty-one studies conducted during the 2006/07-2019/20 influenza seasons were included in the qualitative review; 16 in the meta-analyses. Meta-analysis of test-negative studies found that aTIV reduced medical encounters due to lab-confirmed influenza with pooled estimates of 40.7% (95% CI: 21.9, 54.9; I = 0%) for non-emergency outpatient visits and 58.5% (40.7, 70.9; I = 52.9%) for hospitalized patients. The pooled estimate of VE from case-control studies was 51.3% (39.1, 61.1; I = 0%) against influenza- or pneumonia-related hospitalization. The pooled estimates for the relative VE of aTIV for the prevention of influenza-related medical encounters were 13.9% (4.2, 23.5; I = 95.9%) compared with TIV, 13.7% (3.1, 24.2; I = 98.8%) compared with QIV, and 2.8% (-2.9, 8.5; I = 94.5%) compared with HD-TIV.
CONCLUSIONS
Among adults ≥65 years, aTIV demonstrated significant absolute VE, improved relative VE compared to non-adjuvanted standard-dose TIV/QIV, and comparable relative VE to high-dose TIV.
Topics: Adjuvants, Immunologic; Adult; Aged; Humans; Influenza Vaccines; Influenza, Human; Polysorbates; Seasons; Squalene
PubMed: 34081398
DOI: 10.1111/irv.12871 -
Journal of Oleo Science 2024Medium-chain triacylglycerol (MCT) is a type of triacylglycerol that has six or seven to twelve carbon chains. It consists of three molecules of fatty acids attached to...
Medium-chain triacylglycerol (MCT) is a type of triacylglycerol that has six or seven to twelve carbon chains. It consists of three molecules of fatty acids attached to one molecule of glycerol. Drug delivery system (DDS) is defined as a formulation to distribute drugs into the human body. The unique properties of MCTs have garnered interest in using them as excipients in DDS. Even though there are many significant effects attributed to the use of MCTs, especially in modulating the rate of drug delivery in various DDS, they are all limited and intermittent. This warrants a detailed summary of the previous studies on the use of MCTs in various DDS. Therefore, this review focuses on presenting a systematic review of previous studies on the use of MCTs in the last six years and explores the types and effects of MCTs on DDS that employ various types of delivery routes. A systematic search through PubMed, Science Direct and Scopus was performed. Keywords like "medium-chain triglycerides", "medium-chain fatty acids", "medium-chain triglycerides and their fractions", "medium-chain fatty acids and their fractions", "MCTs", "MCFA", "in drug delivery", "in drug delivery system" and their combinations were used. The synonyms of the words were also used to extend the search. A total of 17 articles that met the inclusion criteria were identified. Findings from this review have identified the several MCTs and their fractions used in DDS that employed the oral/enteral, topical, transdermal, parenteral, and pulmonary routes of drug delivery. The review also highlights that the usage of MCTs in DDS results in a better transportation of drugs into the human body.
Topics: Humans; Drug Delivery Systems; Carbon; Excipients; Fatty Acids; Triglycerides
PubMed: 38432994
DOI: 10.5650/jos.ess23204 -
Human Vaccines & Immunotherapeutics 2019Seasonal influenza is a very common disease. Yearly vaccination of at-risk population groups is a well-recognized cost-effective/cost-saving preventive measure. It is,...
Seasonal influenza is a very common disease. Yearly vaccination of at-risk population groups is a well-recognized cost-effective/cost-saving preventive measure. It is, however, unclear which available alternative has the most favorable economic profile. Some available options are: trivalent (TIV) and quadrivalent (QIV) inactivated vaccines, adjuvanted TIV (aTIV). Because of immunosenescence, aTIV has been specifically developed for elderly. The present study aimed at assessing the available evidence of aTIV use in elderly from the economic perspective. A systematic literature review targeting aTIV economic evaluations in adults aged ≥65 years was performed using Medline via Ovid, Embase, DARE and NHS/EED. Of a total of 3,654 papers screened, 18 studies (13 full papers, 5 conference abstracts) were included. It emerged that compared with both non-vaccination or non-adjuvanted vaccines, aTIV was cost-effective or cost-saving. The vaccinations strategies incorporating aTIV based on age and/or risk profile are associated with the most favorable economic outcomes.
Topics: Adjuvants, Immunologic; Age Factors; Aged; Aged, 80 and over; Antibodies, Viral; Cost-Benefit Analysis; Humans; Influenza Vaccines; Influenza, Human; Polysorbates; Risk Factors; Squalene; Vaccination
PubMed: 30735465
DOI: 10.1080/21645515.2019.1578597