Depot, drug administration

Restricted diffusion also limits tissue distribution after intraparenchymal drug administration, as shown in Figure 2.7c and d. Distribution has been measured in the rat brain after implantation of polymer discs containing NGF [66]. Drug concentrations decreased to less than 10% of the values measured on the disc surface within a distance of 2-3 mm, even after prolonged periods of several days. Therefore, applying this approach in the larger human brain would require the stereotaxic placement of multiple intraparenchymal depots, as has been evaluated in rat brain [67], on a repetitive schedule. 

Metrikin, D.C. and Anand R. (1994) Intravitreal drug administration with depot devices. Current Opinion in Ophthalmology, 5 21-29. 

From pharmacology results and proposed clinical program, select route of administration (oral, pulmonary, intramuscular, subcutaneous, transdermal, ocular, vaginal, buccal, sublingual, etc.) and formulation type to be dosed (solution, suspension, tablet, capsule, granulation powder, microspheres, microemulsion, depot drug, etc.). 

Okada and co-workers (1988,1989,1991) and Ogawa etal. (1988) have also described a 75 25 PLGA microencapsulated 30-day release system for the delivery of another LHRH analog leuproUde acetate [(D-Leu , Pro NEt)-LHRH Lupron Depot , Takeda-Abbott], Their results indicate that a single injection of microcapsules maintains constant and effective serum levels of the analog for one month. Sufficient therapeutic efficacy in the treatment of advanced prostatic cancer has also been shown for leuprolide acetate, and the product has recently been approved for use by the U.S. Food and Drug Administration (Lupron Depot , 7.5mg PDR, 1994). This treatment has also shown to cause a dramatic regression of... 

Drug administration route There is a greater risk of developing ketoacidosis with insulin-pump therapy than with multiple daily insulin injections, because there is always a smaller subcutaneous depot of insulin at any time with the insulin pump. However, in practice, the frequency of ketoacidosis is similar with insulin pump and insulin injections. Insulin-pump therapy can lead to some localised non-serious skin infections at the infusion site. In general, current pumps are robust and reliable, but malfunctions can still occur. [15 ]... 

Factors known to influence the clearance of drugs from interstitial sites, following extravasation or parenteral interstitial or transepithelial administration, include size and surface characteristics of particles, formulation medium, the composition and pH of the interstitial fluid, and disease within the interstitium. Studies indicate that soluble macromolecules smaller than 30 nm can enter the lymphatic system, whereas particulate materials larger than 50 nm are retained in the interstitial sites and serve as a sustained-release depot. The use of lipids or an oil in a formulation and the presence of a negative surface charge all appear to... 

Many drugs are administered as parenterals for speed of action because the patient is unable to take oral medication or because the drug is a macromolecule such as a protein that is unable to be orally absorbed intact due to stability and permeability issues. The U.S. Pharmacopoeia defines parenteral articles as preparations intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal. They include intravenous, intramuscular, or subcutaneous injections. Intravenous injections are classified as small volume (<100 mL per container) or large volume (>100 mL per container) injections. The majority of parenteral dosage forms are supplied as ready-to-use solutions or reconstituted into solutions prior to administration. Suspension formulations may also be used,101 although their use is more limited to a subcutaneous (i.e., Novolin Penfill NOVO Nordisk) or intramuscular (i.e., Sandostatin LAR Depot Novartis) injection. Intravenous use of disperse systems is possible but limited (i.e., Doxil Injection Ortho Biotec). 

The advantages of administration by intramuscular injection are that the muscle can act as a depot, and the rate of disappearance of drug from the site of injection can be calculated. Inhalational, intranasal, and intratracheal administration are normally reserved for vapors and aerosols including anesthetics. Absorption is facilitated by small-sized particles, high lipid solubility, sufficient pulmonary blood flow, and a large absorptive surface area, as it is present in healthy lungs. Administration by these routes can be very rapid when several of the factors favoring increased absorption are combined. 

Conversely, certain forms of intramuscular antipsychotics that enter the bloodstream slowly have been developed. This method of depot administration may prove helpful if the patient has poor selfadherence to drug therapy and neglects to take his or... 

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