International journal of clinical practice. Supplement
-
When Exubera (EXU), the first inhaled insulin formulation to make it through the clinical development process, was introduced to the market some years ago it was hoped that this would be the first in a series of novel insulin formulations applied by this route. In addition, it was hoped that inhaled insulin would pave the way for other alternative routes of insulin administration (ARIA), i.e. oral insulin, nasal insulin or transdermal insulin to mention only some of the different attempts that have been studied in the last 90 years. The failure of EXU, i.e. its withdrawal from the market due to insufficient market success, was followed by the cessation of nearly all other attempts to develop inhaled insulin formulations. ⋯ Nevertheless, this is the route of insulin administration where I would put my money (if I had enough). Also in this area of research it is not easy to make statements about which approaches are valid and will make it to a product. The fact that some large pharmaceutical companies are active in this area indicates that they also believe that oral insulin is the hottest candidate of the next ARIA that will come to the market.
-
Int J Clin Pract Suppl · Jul 2008
ReviewRight heart function and haemodynamics in pulmonary hypertension.
The primary challenge in the care of the patient with advanced pulmonary arterial hypertension (PAH) is right ventricular dysfunction with concomitant right heart failure. Right heart function is closely tied to survival in this disease, and there is a growing interest in the study of this unique structure. ⋯ Several of the currently available treatments for PAH have been shown to have effects on the RV, not just the pulmonary vasculature, and, in future, therapies aimed at optimizing right ventricular function may allow better outcomes in this challenging disease. New directions in right ventricular assessment including measurement of pulmonary vascular impedance and more widespread availability of CMR may allow greater knowledge about this little studied, yet highly important, right side of the heart.
-
Pulmonary hypertension (PH) may complicate the course of many forms of advanced interstitial lung disease (ILD) and has been shown to portend a worse outcome. The aetiology of PH is likely multifactorial with variable contribution of factors amongst the different diseases. The most common such conditions include idiopathic pulmonary fibrosis, sarcoidosis, connective tissue disease-related ILD and pulmonary langerhans cell histiocytosis. Whether the course and impact of PH in these conditions can be modified by therapy requires further study.
-
Int J Clin Pract Suppl · Sep 2007
ReviewPulmonary hypertension and the serotonin hypothesis: where are we now?
In the 1960s, serotonin (5HT) was associated with pulmonary arterial hypertension (PAH) caused by certain diet pills, but has recently been the subject of renewed interest in the field of PAH. Serotonin can be synthesised in the pulmonary endothelium with the rate-limiting step being the activity of tryptophan hydroxylase1 (Tph1). ⋯ Here we will unravel, discuss and update the 'serotonin hypothesis' of PAH in light of recent advances in the field. In conclusion, the activity of serotonin receptors, the SERT and Tph1 can all be elevated in clinical and experimental PAH and each offers a potentially unique therapeutic target.
-
Int J Clin Pract Suppl · Dec 2005
ReviewDo all dry powder inhalers show the same pharmaceutical performance?
Important measures of pharmaceutical performance of dry powder inhalers include total emitted dose (TED, the quantity of drug emitted from the device when used at a fixed flow rate, typically 60 l/min or the flow rate achieved at a pressure drop of 4 kPa) and fine particle mass (FPM, the quantity of drug with small particles, typically with an aerodynamic diameter of less than 5 microns emitted from the device at a fixed flow rate). There is a wide range of dry powder inhalers available. ⋯ It is not surprising therefore that evidence from in vitro studies shows considerable variation in pharmaceutical performance of dry powder inhalers. Although neither TED nor FPM can accurately predict in vivo performance, it may be expected that highly variable or inhalation flow sensitive in vitro behaviour will be reflected in variable performance when used by patients.