Administration route accessibility

Which route of administration is optimum Choosing the optimum dmg administration route takes into account the specific circumstances of each individual case. For example, can the patient tolerate oral medications, or is intravenous administration required Does the patient have venous access For how long can it be maintained Is intramuscular administration a possibility In many clinical situations, the available formulation determines the route of administration. Antibiotics are a prime example of this phenomenon ceftriaxone, for example, is available only for parenteral administration while amoxicillin is administered orally. 

In general, the administration route plays an important role on the impact of the therapeutic treatment, and it is chosen according to the kind or purpose of the treatment (local or systemic), toxicity, and accessibility of the diseased area. In this section specific characteristics of other routes of administration that are currently receiving attention will be emphasized and the most recent developments with respect to liposomal drug applications will be presented. 

As previously mentioned, systemic delivery is limited because of the isolation of ocular tissues from the systemic circulation thus, topical delivery is often the preferred administration route owing to ease of access and patient compliance, particularly when treating infections of the anterior segment such as keratitis sicca, conjunctivitis, or blepharitis and diseases such as glaucoma or uveitis that require the drug to be diffused across the corneal barrier [19,20]. However, drainage, lacrimation and tear dilution, tear turnover, conjunctival absorption, and the corneal epithelium all limit corneal drug penetration [21,22]. 

In a multicentre observational study to examine the association between administration route or place of insertion of central venous catheters and the incidence of CRI in patients on TPN, there was no significant association between the site of venous access and the incidence of infections. There was a significant relationship between the insertion procedure and incidence of CRI (P=0.0007), with very low incidence rates observed in patients in intensive care units compared with other hospital departments [125 ]. 

The route of antigen administration can alter the speed of antigen access to the circulation and, thus, the systemic symptoms in anaphylaxis models. For example, allergen ingestion typically induces anaphylaxis that includes gastrointestinal symptoms, such as diarrhea [4]. These intestinal anaphylaxis models in mice are dependent on IgE-induced mast cell activation, and the release of PAF and serotonin (rather than histamine) [1,4]. 

Subcutaneous (SC) administration of ESA produces a more predictable and sustained response than IV administration, and is therefore the preferred route of administration for both agents. Intravenous administration is often utilized in patients who have established IV access or are receiving hemodialysis. Starting doses of ESAs depend on the patient s Hgb level, the target Hgb level, the rate of Hgb increase and clinical circumstances.31 The initial increase in Hgb should be 1-2 g/dL (0.6206-1.2404 mmol/L) per month. The starting doses of epoetin alfa previously recommended are 80 to 120 units/kg per week for SC administration and 120 to 180 units/kg per week for IV administration, divided two to three times per week. The starting dose of darbepoetin alfa is 0.45 mcg/kg administered SC or IV once weekly (Table 23-3). 

It might be expected that EN via tubes would have been used widely before the development of parenteral nutrition (PN) however, this was not actually the case. EN via tubes inserted down the mouth or nose into the stomach and also via rectal tubes was used occasionally in the decades before the development of PN in the 1960s.1 However, modern techniques for enteral access, both the placement of the tubes themselves and the materials for making pliable, comfortable tubes, had not yet been developed. Before the PN era, the formulas delivered by the tube route often were blenderized foods. The National Aeronautics and Space Administration effort in the United States in the 1960s led to the development of low-residue (monomeric) diets for astronauts. These diets were adapted for use in sick patients requiring EN. Nonvolitional feedings in patients who cannot meet nutritional requirements by oral intake thus include EN and PN these techniques are collectively known as specialized nutrition support (SNS). 

In the IV route, anaphylactic reactions (caused by administration of an agent to an animal previously sensitized to it or to a particularly sensitive species such as a guinea pig) may be especially severe, probably because of sudden, massive antigen-antibody reactions. When the drug is given by other routes, its access to antibody molecules is necessarily slower moreover, its further absorption can be retarded or prevented at the first sign of a serious allergic reaction. 

BioPrint consists of a large database and a set of tools with which both the data and the models generated from the data can be accessed. The database contains structural information, in vivo and in vitro data on most of the marketed pharmaceuticals and a variety of other reference compounds. The in vitro data generated consist of panels of pharmacology and early ADME assays. The in vivo data consist of ADR data extracted from drug labels, mechanisms of action, associated therapeutic areas, pharmacokinetic (PK) data and route of administration data. 

In general, when the cells of the endothelium in the lungs are the target cells of interest (see Chapters 7 and 9 on aspects of targeting drugs to endothelium in inflammatory diseases and cancer, respectively), systemic administration seems the route of choice. Bronchial epithelium on the other hand can more easily be reached via the pulmonary route. The accessibility of other cells in the lungs is most hkely governed by disease conditions, factors that can affect epithehal permeability and vascular permeability, and others as described earher. 

It is sometimes possible to get an indication of how widely the parent compound may distribute in the body from the available physico-chemical data. The sites to which the parent compound distributes (pattern of distribution) once it has entered the systemic circulation are likely to be similar for all routes of administration. In general, substances and their metabohtes that readUy diffuse across membranes wUl distribute throughout the body and may be able to cross the blood-brain and blood-testes barriers, although the concentrations within the brain or testes may be lower than that in the plasma. The rate at which highly water-soluble molecules distribute may be hmited by the rate at which they cross cell membranes and access of such substances to the central nervous system (CNS) or testes is likely to be restricted (though not entirely prevented) by the blood-brain and blood-testes barriers. 

While some parenteral injections, such as intravenous administration, provide rapid and predictable access to the circulation and tissues, therapeutic proteins are rapidly cleared from the system, and thus such administrations may result in very short durations of action. Regardless of route of administration, therapeutic proteins may exhibit limited distribution outside of endothelial cells lining blood vessels. This may be advantageous for thrombolytic agents, such as tissue plasminogen activator, which is used for rapid fibrinolytic actions at... 

---