Inhaled clinical studies

If oncogenicity studies have been conducted by the oral route and another clinical route is to be used in man, the need to repeat such studies should be assessed critically. Oncogenic potential is related to the concentration of the carcinogen at its site of action. Thus, if the oral route results in adequate exposure of the lung, there should be no need to perform additional inhalation oncogenicity studies. Inhalation studies of 1-3 months duration should be performed to assess possible local effects on respiratory tissue and also to gain pharmacokinetic data. 

Although no biopharmaceutical product delivered to the bloodstream via the pulmonary route has been approved to date, several companies continue to pursue active research and development programmes in the area. Amongst the leading product candidates is Exubera , an inhalable dry powder insulin formulation currently being evaluated by Pfizer and Aventis Pharma in Phase III clinical studies. The inhaled insulin is actually more rapidly absorbed than if administered subcutaneously and appears to achieve equivalent glycaemic control. While promising, final approval or otherwise of this product also depends upon additional safety studies which are currently under way. 

Different clinical studies suggest that inhalation or contact with aeroal-lergens (especially house dust mites) may exacerbate AD [reviewed in 38]. Nevertheless, there are very few studies regarding the treatment of AD. 

In a multi-center, two-year clinical study, inhaled domase-oc was shown to significantly improve lung function and reduce the risk of respiratory exacerbations in pediatric cystic fibrosis patients [25]. 

In special studies, such as inhalation toxicity studies, the entire respiratory tract should be studied, including the nose, pharynx, and larynx. If other clinical examinations are performed, the information obtained from these procedures should be available before microscopic examination, because it may give significant guidance to the pathologist. 

Several other therapeutic effects of sodium channel blockers have been suggested. Most of these stem from clinical activities of approved anticonvulsants and antiarrhythmics with sodium channel blocking activity. Beneficial effects of sodium channel blockers for the treatment of bipolar disease are suggested by clinical data with lamotrigine [63-67], phenytoin [68], topiramate [69], and carbamazepine [70,71]. In addition, clinical studies with lidocaine suggest efficacy in the treatment of tinnitus [72] and, as an inhaled formulation, in the suppression of cough [73,74]. 

Berelowitz, M. Becker, G. Inhaled insulin—clinical pharmacology and clinical study results. In Respiratory Drug Delivery VIP, Dalby, R.N., Byron, P.R., Farr, S.J., Peart, J., Eds. Serentec Press, Inc. Raleigh, NC, 2000 151-154. 

Sulfobutylether P-cyclodextrin is included in IV and IM injectable products currently approved and marketed in the USA and Europe. It is included in the FDA inactive ingredient guide for IM and IV use. Its use by other routes, including oral, inhalation, and ophthalmic, is being evaluated in clinical studies. 

Historically, injuries and fatalities have been reported from acute methanol overexposure via ingestion, inhalation, as well as prolonged or repeated skin contact. Inhalation toxicity can occur in occupational settings or as a result of inhalant abuse (huffing). Clinical studies of individuals acutely poisoned by methanol ingestion have identified visual disturbances and possibly blindness as the most notable toxic effects in humans. Methanol is also a CNS depressant, although less potent than ethanol, and has also been shown to produce liver damage upon overexposure. 

A wide variety of nebulizers are now available. They all have their own physicochemical properties. In the absence of the ability to quantitate lung deposition, most modem labels specify the combination of a new dmg with particular nebulizer device (the labeling for alpha-domase was the first to exhibit this change in regulatory policy). The corollary is that product development plans should decide, as early as possible, which nebulizer is intended for the marketplace, and that device should be used in all inhalational toxicology studies and subsequent clinical trials. 

---