Administration route ideal

Within the chapters, the reader may find the same enhancer tested for various administration routes and in diverse experimental models. By understanding the properties and behavior of the accelerants operating within such systems, the scientist may be inspired with new ideas for choosing the ideal promotor for a new application. The contributing authors, in their reviews, discuss not only the achievements, but also the failures and drawbacks of various enhancers that are often mainly related to their toxicities. 

Drug administration route The authors compared a new and old adrenaline autoinjector with respect to correct autoinjector use. The new adrenaline autoinjector is more effective in unintentional injection injuries than the old one however, it still does not fulfil the criteria of an ideal adrenaline autoinjector [24 ]. 

Research studies investigating exposure to JP-8 via oral administration offers an alternative examination of the systemic effects of JP-8 on immune function. Admittedly, this does not ideally mimic occupational exposures, but it does eliminate technical limitations associated with inhalation and dermal penetration of JP-8. It has been suggested that the only route available that can assess the whole mixture (JP-8 in its entirety), without fractionation due to volatilization of components, is the oral route [1] as select components of JP-8 may have increased permeability during dermal exposure, other specific components may be enriched following inhalation exposures[71]. 

Phil Kysor and I similarly developed a TRI to represent a subject s response to BZ. We combined changes in blood pressure (BP), heart rate (HR) and performance on Number Facility (NF), using a scale from 1- 9 for each variable. It helped us to compare responses to BZ given by various routes of administration. Eventually we could combine intravenous, intramuscular, oral, inhalation and percutaneous responses using the TRI as an indicator of relative effectiveness. Fig. 4 shows idealized response curves for various intensities of BZ response. 

Ideally, toxicology studies should mimic, as near as possible, human exposure. Thus, both the route of administration and the exposure should, where possible, be similar to that in man. The classic route of administration in man is oral and thus most toxicology studies are conducted by the oral route. Elowever, parenteral routes may be used either to mimic the clinical route or to ensure exposure. The administration of some medicines is directly on to highly differentiated surfaces such as the alveolar surface of the lungs or the skin. It is, therefore, important to assess the topical irritancy, absorption and subsequent systemic toxicity following such applications. It should be remembered that some compounds, for example, chlorinated hydrocarbons, may be more toxic when given by the inhalation route than when given orally or may directly affect... 

The clinical development plan to be supported would be idealized, with minimal delays between phases and without substantive changes to the test article (e.g., no changes to manufacturing process or formulation) or the route of administration. 

Ideally preclinical safety evaluation studies should be designed based on the intended clinical route of administration using the intended clinical delivery device (if applicable). 

When assessing the potential routes of administration, one must consider the physicochemical properties of the drug, its ADMET properties, the therapeutic indication, and the patient population, some of which are discussed below. Table 1 provides a list of some of those factors that must be addressed when determining the most favorable route of administration and the subsequent formulation for delivery. Ideally the route of administration and subsequent formulation will be optimized after identifying critical design parameters to satisfy the needs of patients and health care professionals alike while maintaining the safety and efficacy of the product. 

The critical study (Bucci and Parker 1992) involved a relevant route of exposure (oral) for determining an RfD. Rats were administered GB by oral gavage, a route of administration that exaggerates the exposure that would normally occur from methods resulting in a slower rate of delivery (e.g., in feed or water). However, the study was subchronic in duration (13 weeks) rather than chronic (104 weeks), and ChE measurements varied and did not show a consistent dose-response relationship across ChE types and genders. Thus, the subcommittee believes that the study was too short in duration and that the results were too variable to form an ideal basis for determining a LOAEL. In addition, the methods used to measure ChE were not ideal (see Appendix G). However, in the absence of other well-conducted studies, the subcommittee agrees with ORNL that the study by Bucci and Parker (1992) is the most appropriate of the available studies for derivation of the RfD for GB. 

Ideally the effective dose should be used for the shortest time necessary to secure the desired clinical response. The dosage should be individualized as much as possible to the patient and the severity of the condition. The patient s general health must be considered and close supervision maintained to assess the effects of steroid therapy on the course of the disease and possible adverse effects. With ocular disease the route of steroid administration is an important determinant of the pharmacologic and therapeutic effects observed. Topical ocular therapy is usually satisfectory for inflammatory disorders of the eyelids, conjimctiva, cornea, iris, and ciliary body. In severe fiarms of anterior uveitis, topical therapy may require supplementation with systemic or periocular (local injection) steroids. Chorioretinitis and optic neuritis are most often treated with systemic steroids. 

Because poor bioavailability represents one of the principal causes of compound failure, absorption and metabolism assays feature prominently in lead optimization screens. As oral administration represents the ideal route of drug delivery, models that predict low absorption across the gastrointestinal (GI) tract are commonly employed. Caco-2 cell assays have been... 

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