CONSIDERATIONS FOR TOXICOLOGY STUDIES OF RESPIRATORY DRUG PRODUCTS

The standard approaches for the preclinical development of chronically administered drugs also apply to most respiratory drugs. Modification s from the standard preclinical development plan, however, may be nece ssary if the drug is administered intranasally or by inhalation. Admin istration by these routes may result in airway toxicity and the intend ed patient population is often particularly susceptible. Current and f ormer representatives of the Division of Pulmonary Drug Products (CDER , U.S. FDA) present this article to describe general principles of pre clinical development for respiratory drug indications. The article add resses drugs intended for administration by the intranasal or inhalati on routes. The article describes the types of studies recommended, con siders the initial human dose, and discusses dose-escalation strategie s in clinical trials. Other areas of special concern with intranasal o r inhalation administration include immunotoxicity, reproductive toxic ity, types of dosing apparatus, excipients and extractables, and formu lation changes. The approaches described in this article are intended as general information and should be adapted to the scientific conside rations and circumstances of a particular drug under development. (C) 1997 Academic Press.