Expert review of clinical pharmacology
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Expert Rev Clin Pharmacol · Jul 2017
ReviewA consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus.
The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus. Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin. ⋯ Dapagliflozin can be utilized in combination with all other antihyperglycaemic agents at all stages of the disease: however, a reduced GFR limits its efficacy. As for the other drugs of the class, Dapagliflozin positively modifies other risk factors for CV disease: these effects will be tested in the so far largest cardiovascular outcome trial for the SGLT2 inhibitors so far, the DECLARE trial, which will communicate whether this class of drugs will be disease-modifier in patients with type 2 diabetes also in primary prevention.
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Expert Rev Clin Pharmacol · Jul 2017
ReviewSelexipag, a selective prostacyclin receptor agonist in pulmonary arterial hypertension: a pharmacology review.
Pulmonary hypertension is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest. Management of pulmonary arterial hypertension (PAH) includes specific drug therapy with calcium channel blockers in vasoreactive patients, or drugs approved for PAH in non-reactive patients that target the endothelin, nitric-oxide and prostacyclin pathways. Areas covered: The review covers receptor selectivity, pharmacokinetics, pharmacodynamics and adverse effects (AEs) of intravenous (IV) epoprostenol (synthetic prostacyclin); the prostacyclin analogs iloprost, beraprost, and treprostinil administered by IV, subcutaneous, inhaled or oral routes; and the oral selective prostacyclin receptor agonist selexipag. ⋯ The high selectivity of selexipag, and its active metabolite ACT-333679, for the prostacyclin receptor, in conjunction with pharmacokinetic properties that reduce peak-trough fluctuations and the up-titration regimen used at the start of treatment, are collectively considered to minimize AEs associated with prostacyclin use. In a large phase 3 study, selexipag-associated AEs were consistent with those observed with drugs that target the prostacyclin pathway, and mainly mild to moderate in severity. The dosing flexibility afforded by oral selexipag may facilitate achieving the maximum therapeutic effect with acceptable tolerability in patients with PAH.
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Expert Rev Clin Pharmacol · Jul 2017
GFF MDI for the improvement of lung function in COPD - A look at the PINNACLE-1 and PINNACLE-2 data and beyond.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and incidence rates are continuing to rise. Long-acting bronchodilators are the foundation on which current pharmacological approaches to COPD management are built, with long-acting muscarinic antagonists (LAMAs) and long-acting β2-agonists (LABAs) recommended across the spectrum of the disease continuum. Combining LAMAs and LABAs provides additional lung function improvements and relief of patient symptoms compared with either therapy alone. ⋯ Areas covered: This article describes the rationale for the development of the LAMA/LABA FDC of glycopyrrolate and formoterol fumarate, formulated by Co-Suspension™ Delivery Technology and delivered by MDI (GFF MDI). The clinical trial program of GFF MDI, including the pivotal Phase III studies (PINNACLE-1 and PINNACLE-2) that supported regulatory approval, are reviewed, providing insights into interpretation and future directions for research. Expert commentary: LAMA/LABA FDCs are already a crucial part of the COPD treatment paradigm, but additional data are needed in order to maximize their role as maintenance therapies in patients with COPD.