| 1. |
- Henrohn, Dan, et al.
(författare)
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Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension
- 2012
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley-Blackwell. - 0306-5251 .- 1365-2125. ; 74:6, s. 990-998
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Tidskriftsartikel (refereegranskat)abstract
- AIMS To evaluate the acute haemodynamic effects of a single oral dose of vardenafil and to study the drug concentration in relation to haemodynamic effects in patients with pulmonary hypertension (PH). METHODS Sixteen patients with PH (aged 29-85\ years), received one single oral dose of vardenafil (5, 10 or 20 mg). The haemodynamic effect was assessed over a 60 min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60 min using liquid chromatography-tandem mass spectrometry. RESULTS At 60 min a reduction in mPAP with a median % decrease of -20.3% (range -48.3 to 3.0; P < 0.001) and an increase in cardiac output and the cardiac index with a median % change of 10.6% (range -25.0 to 88.1; P = 0.015) and 12.1% (range -24.0 to 94.4; P = 0.01) respectively was observed. The pulmonary vascular resistance (PVR) was reduced with a median % decrease of -28.9% (range -61.5 to -5.9; P < 0.001), and pulmonary selectivity was reflected by a median percent reduction of -16.9% (range -49.0 to 16.5; P = 0.002; n = 14) in the PVR/ systemic vascular resistance ratio. There was a correlation between the plasma concentrations of vardenafil and change in mPAP (r = -0.579, P = 0.019) and between vardenafil concentrations and change in PVR (r = -0.662, P = 0.005). CONCLUSIONS Vardenafil causes rapid changes in cardiopulmonary haemodynamics and there is a correlation between plasma vardenafil drug concentration and the acute changes in mPAP as well as PVR in patients with PH.
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| 2. |
- Bytyci, Ibadete, et al.
(författare)
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Efficacy and safety of colchicine in patients with coronary artery disease : a systematic review and meta-analysis of randomized controlled trials
- 2022
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Ingår i: British Journal of Clinical Pharmacology. - : British Pharmacological Society. - 0306-5251 .- 1365-2125. ; 88:4, s. 1520-1528
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Forskningsöversikt (refereegranskat)abstract
- Aims: Inflammation plays a central role in the pathogenesis and clinical manifestations of atherosclerosis. Randomized controlled trials have investigated the potential benefit of colchicine in reducing cardiovascular (CV) events in patients with coronary artery disease (CAD) but produced conflicting results. The aim of this meta-analysis was to evaluate the efficacy and safety of colchicine in patients with CAD.Methods: We systematically searched selected electronic databases from inception until 10 December 2020. Primary clinical endpoints were: major adverse cardiac events; all-cause mortality; CV mortality; recurrent myocardial infarction; stroke; hospitalization; and adverse medication effects. Secondary endpoints were short-term effect of colchicine on inflammatory markers.Results: Twelve randomized controlled trials with a total of 13 073 patients with CAD (colchicine n = 6351 and placebo n = 6722) were included in the meta-analysis. At mean follow-up of 22.5 months, the colchicine group had lower risk of major adverse cardiac events (6.20 vs. 8.87%; P <.001), recurrent myocardial infarction (3.41 vs. 4.41%; P =.005), stroke (0.40 vs. 0.90%; P =.002) and hospitalization due to CV events (0.90 vs. 2.87%; P =.02) compared to the control group. The 2 patient groups had similar risk for all-cause mortality (2.08 vs. 1.88%; P =.82) and CV mortality (0.71 vs. 1.01%; P =.38). Colchicine significantly reduced high-sensitivity C-reactive protein (−4.25, P =.001) compared to controls but did not significantly affect interleukin (IL)-β1 and IL-18 levels.Conclusion: Colchicine reduced CV events and inflammatory markers, high-sensitivity C-reactive protein and IL-6, in patients with coronary disease compared to controls. Its impact on cardiovascular and all-cause mortality requires further investigation.
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| 3. |
- Curry, S H, et al.
(författare)
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Pharmacokinetics of closely related benzodiazepines.
- 1979
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Ingår i: British Journal of Clinical Pharmacology. - 0306-5251 .- 1365-2125. ; 8:1, s. 15S-21S
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Tidskriftsartikel (refereegranskat)abstract
- 1 It is commonplace for drugs to vary by only minor chemical differences. This is particularly so for those seven benzodiazepines discussed in this paper which are related both as precursors and as metabolites. However, minor chemical differences may cause major differences in physicochemical and pharmacodynamic properties. 2 Although the physicochemical differences are difficult to relate to effect, the influence of structure on absorption, distribution and elimination is of considerable importance in governing duration of effect, as shown by studies in monkeys and in man. This in turn dictates the suitability of a particular drug as a day or night sedative, as an anticonvulsant, or as an anxiolytic. 3 Structure affects the relative potency of the compounds as anticonvulsants, anxiolytics or sedatives so that judicious choice of a particular compound for a particular patient and condition will lead to improved therapy. It is fallacious to consider all benzodiazepines as similar.
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| 4. |
- Gabrielsson, Linda, et al.
(författare)
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Palmitoylethanolamide for the treatment of pain : pharmacokinetics, safety and efficacy
- 2016
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 82:4, s. 932-942
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Forskningsöversikt (refereegranskat)abstract
- Palmitoylethanolamide (PEA) has been suggested to have useful analgesic properties and to be devoid of unwanted effects. Here, we have examined critically this contention, and discussed available data concerning the pharmacokinetics of PEA and its formulation. Sixteen clinical trials, six case reports/pilot studies and a meta-analysis of PEA as an analgesic have been published in the literature. For treatment times up to 49days, the current clinical data argue against serious adverse drug reactions (ADRs) at an incidence of 1/200 or greater. For treatment lasting more than 60days, the number of patients is insufficient to rule out a frequency of ADRs of less than 1/100. The six published randomized clinical trials are of variable quality. Presentation of data without information on data spread and nonreporting of data at times other than the final measurement were among issues that were identified. Further, there are no head-to-head clinical comparisons of unmicronized vs. micronized formulations of PEA, and so evidence for superiority of one formulation over the other is currently lacking. Nevertheless, the available clinical data support the contention that PEA has analgesic actions and motivate further study of this compound, particularly with respect to head-to-head comparisons of unmicronized vs. micronized formulations of PEA and comparisons with currently recommended treatments.
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