Journal: British journal of clinical pharmacology
148
Blood pressure lowering effects of sulodexide depend on albuminuria severity: Post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies
- OPEN
- British journal of clinical pharmacology
- Published over 4 years ago
- Discuss
It has been suggested that sulodexide is able to lower blood pressure (BP). This may be attributed to sulodexide’s ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP lowering potential of sulodexide.
141
Acid suppression medications and bacterial gastroenteritis: a population-based cohort study
- OPEN
- British journal of clinical pharmacology
- Published about 4 years ago
- Discuss
To investigate whether acid suppression medicines (ASMs) increase the risk of bacterial gastroenteritis.
138
Cannabis, from Plant to Pill
- OPEN
- British journal of clinical pharmacology
- Published almost 3 years ago
- Discuss
The therapeutic application of Cannabis is attracting substantial public and clinical interest. The Cannabis plant has been described as a veritable ‘treasure trove’, producing more than a hundred different cannabinoids, although the focus to date has been on the psychoactive molecule delta-9-tetraydrocannabinol (THC) and cannabidiol (CBD). Other numerous secondary metabolites of Cannabis the terpenes, some of which share the common intermediary geranyl diphosphate (GPP) with the cannabinoids, are hypothesised to contribute synergistically to their therapeutic benefits, an attribute that has been described as the ‘entourage effect’. The effective delivery of such a complex multicomponent pharmaceutical relies upon the stable genetic background and standardised growth of the plant material, particularly if the raw botanical product in the form of the dried pistillate inflorescence (flos) is the source. Following supercritical CO2 extraction of the inflorescence (and possibly bracts), the secondary metabolites can be blended to provide a specific ratio of major cannabinoids (THC:CBD) or individual cannabinoids can be isolated, purified and supplied as the pharmaceutical. Intensive breeding strategies will provide novel cultivars of Cannabis possessing elevated levels of specific cannabinoids or other secondary metabolites.
135
The Impact of CYP2D6 mediated Drug-Drug Interaction: A Systematic Review on a Combination of Metoprolol and Paroxetine/Fluoxetine
- OPEN
- British journal of clinical pharmacology
- Published over 2 years ago
- Discuss
Metoprolol (a CYP2D6 substrate) is often co-prescribed with paroxetine/fluoxetine (CYP2D6 inhibitor) because the clinical relevance of this drug-drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the DDI.
80
Incidence and cost of medication harm in older adults following hospital discharge: A multicentre prospective study in the UK
- OPEN
- British journal of clinical pharmacology
- Published almost 3 years ago
- Discuss
Polypharmacy is increasingly common in older adults, placing them at risk of medication-related harm (MRH). Patients are particularly vulnerable to problems with their medications in the period following hospital discharge due to medication changes, and poor information transfer between hospital and primary care. The aim of this study was to investigate the incidence, severity, preventability and cost of medication-related harm (MRH) in older adults in England post-discharge.
55
First-in-human randomised study of bimekizumab, a humanised monoclonal antibody and selective dual inhibitor of IL-17A and IL-17 F, in mild psoriasis
- OPEN
- British journal of clinical pharmacology
- Published over 4 years ago
- Discuss
Assess safety, pharmacokinetics (PK) and clinical efficacy of bimekizumab, (formerly UCB4940), a novel humanised monoclonal antibody and dual inhibitor of interleukin (IL)-17A and IL-17 F, in subjects with mild plaque psoriasis.
42
Cannabidiol for neurodegenerative disorders: important new clinical applications for this phytocannabinoid?
- British journal of clinical pharmacology
- Published almost 9 years ago
- Discuss
Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ(9) -tetrahydrocannabinol is already under clinical evaluation in patients with Huntington’s disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ(9) -tetrahydrocannabinol, i.e. CB(1) and CB(2) receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB(2) receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.
30
Prevalence of Exceeding Maximum Daily Dose of Acetaminophen, and Seasonal Variations in Cold-Flu Season
- British journal of clinical pharmacology
- Published almost 3 years ago
- Discuss
To estimate prevalence of excess intake of acetaminophen, and investigate seasonal variations therein.
29
A systematic review of cannabidiol dosing in clinical populations
- OPEN
- British journal of clinical pharmacology
- Published over 1 year ago
- Discuss
Cannabidiol is a cannabis-derived medicinal product with potential application in a wide-variety of contexts, however its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of cannabidiol in a variety of medical contexts.
29
Grapefruit juice markedly increases the plasma concentrations and antiplatelet effects of ticagrelor in healthy subjects.
- British journal of clinical pharmacology
- Published over 8 years ago
- Discuss
AIM: This study examined the effects of grapefruit juice on the new P2Y(12) inhibitor ticagrelor, which is a substrate of CYP3A4 and P-glycoprotein. METHODS: In a randomized crossover study, ten healthy volunteers ingested 200 ml of grapefruit juice or water thrice daily for four days. On day three, they ingested a single 90-mg dose of ticagrelor. RESULTS: Grapefruit juice increased ticagrelor geometric mean peak plasma concentration (C(max) ) to 165% (95% confidence interval, 147-184%) and area under the concentration-time curve (AUC(0-∞) ) to 221% of control (95% confidence interval, 200-245%). The C(max) and AUC(0-34h) (P < 0.05) but not the AUC(0-∞) of the active metabolite C12490XX were decreased significantly. Grapefruit juice had a minor effect on ticagrelor elimination half-life prolonging it from 6.7 to 7.2 h (P = 0.036). In good correlation with the elevated plasma ticagrelor concentrations, grapefruit juice enhanced the antiplatelet effect of ticagrelor, assessed with VerifyNow® and Multiplate® methods, and postponed the recovery of platelet reactivity. CONCLUSIONS: Grapefruit juice increased ticagrelor exposure by more than two-fold, leading to an enhanced and prolonged ticagrelor antiplatelet effect. The grapefruit juice-ticagrelor interaction seems clinically important and indicates the significance of intestinal metabolism to ticagrelor pharmacokinetics.