Depot-effect

Certain small-volume injections are available where the dmg is dissolved in a viscous oil because it is insoluble in water non-aqueous solvent must be used, hi addition, drags in non-aqueous solvents provide a depot effect, for example for hormonal compounds. The intramuscular route of injection must be used. The vehicle may be a metabolizable fixed oil such as arachis or sesame oil (but not a mineral oil) or an ester such as ethyl oleate which is also metabolizable. The latter is less viscous and therefore easier to administer but the depot effect is of shorter duration. The dmg is normally dissolved in the oil, filtered under pressure and distributed into ampoules. After sealing, the ampoules are sterilized by dry heat, for example, at 160°C for 2 hours. A bactericide is probably ineffective in such a medium and therefore offers very httle protection against contamination in a multidose oily injection. 

Experimental pharmacological investigations into selected acyl enzymes have shown that, besides the depot effect of the modified enzymes, their elimination characteristics changed as did, in some cases, their specific effect, m particular, as for as fibrinolytic enzymes are concerned, acylation could be shown to modify significantly the clearance of these enzymes. The prolonged circulation of... 

In addition, for imaging studies, only liposome-encapsulated gadolinium was used successfully [222, 223], In a more recent study, electron spin resonance (ESR) was applied successfully to investigate the integrity of MLV and the possibility of a depot effect after the s.c. injection in mice [224],... 

For many applications, the mesoporous materials are expected to show enhanced properties when their inner channel walls are functionalized with organic moieties to fine-tune host-guest interactions. This is particularly important for drug delivery systems which require the drug to be released at a slow rate in order to generate the desired depot-effect [19]. 

Furthermore, mesoporous nanoparticles with a diameter of about 100 nm can be produced as shown in the upper part of Fig. 27.5b. We intend to use them as the basis for a novel drug delivery system which is sketched in the lower part of Fig. 27.5b. This system has several functions for controlled release and targeting of specific cells. These functions are (1) functionalized pore walls to create a depot effect and controlled release of the drug ... 

The endotracheal (ET) route has been used to administer medications during CPR when other routes, such as the i.v. route, are unavailable. It provides rapid access as well as rapid drug absorption and distribution.Some studies have shown that the time to reach peak absorption is similar to that for the i.v. route, but serum concentrations achieved were 10-33% of that achieved with i.v. administration, resulting in a weaker response. A depot effect has also been demonstrated for drugs such as epinephrine. Work needs to be done to determine the optimal dose by this route, drug-delivery vehicle, and the most effective delivery technique. 

Corticosteroids also may be delivered by injection. The intramuscular route is preferable in patients with compliance problems, since a depot effect is achieved. Depot forms of corticosteroids include triamcinolone acetonide, triamcinolone hexacetonide, and methylprednisolone acetate. This provides the patient with 2 to 8 weeks of symptomatic control. The depot effect provides a physiologic taper, avoiding withdrawal reaction associated with hypothalamic-pituitary axis suppression. It should be noted that the onset of effect via this route may be delayed by several days. Intravenous corticosteroids may be used to provide the patient with large amounts of drug during a steroid burst to control severe symptoms. Intra-articular injections of depot forms of corticosteroids can be useful in treating synovitis and pain when a small number of joints are affected. The onset and duration of symptomatic relief are similar to those of intramuscular injection. The intra-articular route often is preferred because it is associated with the fewest number of systemic adverse effects. If efficacious, intra-articular injections may be repeated every 3 months. No one joint should be injected more than two to three times per year because of the risk of accelerated joint destruction and atrophy of tendons. Soft tissues such as tendons and bursae also may be injected. This may help control the pain and inflammation associated... 

King, M. T., WQd, D., Gox ke, E., and Eckhardt, K. (1982). 5-Bromo)deoxyutidine tablets with improved depot effect for analysis in vivo of sister-chromatid exchanges in bone-marrow and spermatogonial cells. Mutat Res 97, 117-129. 

The acyl enzyme is an inert form of the enzyme for which—by an intramolecular mechanism—the active enzyme is generated. Therefore, the reversibly acylated enzyme could be used as a delivery system for the active enzyme whose action is both delayed and prolonged in plasma (depot effect). 

The encapsulation of drug molecules also leads to delivery systems, especially in the case of hydrophilic compounds where a permeation barrier with depot effect is provided. The permeation velocity is controlled by the properties of the membranes, as well as by the lipophilicity and size of the incorporated drug. Even large molecules are released slowly in the body, but unfortunately this also occurs under storage conditions. As liposomes do not have a solid surface, an equilibrium is built up between incorporated or adhered drug and free drug molecules, and this can lead to bursf effects when liposome dispersions are diluted. 

Barstad The time course of the experiments makes it unlikely that a residue of inhibitor (or reactivator) high enough to be a serious source of error should persist in the tissues at the time of homogenization. We injected paraoxon intravenously to keep the dose low, thereby avoiding a depot effect. The oximes were administered so as to outlast the inhibitor, and the animals were given 18 h more to get rid of the oximes. 

Because of a highly lipophilic depot effect, salmeterol is retained in the lungs where its actions are desired. After it has finally been released into the systemic circulation, it then becomes very desirable to have GYP450 aggressively attack the molecule by N-dealkylation so as to eliminate it and avoid potential toxicity. Thus, use of a gem-dimethyl arrangement, as depicted earlier, would attenuate the desired N-dealkylation reaction and the desired clearance from the systemic circulation (i.e., thin rather than bulky works best to accelerate a desired metabolism-driven clearance). 

The most widely used parenteral administration avenues are intravenous (iv), intramuscular (im), and subcutaneous (sc). In addition, there are several minor applications (e.g. intraarterial). Application of a protein drug by the different main parenteral administration routes may have profound effects on the pharmacological performances. When the drug is administered iv, it is immediately available for action in the circulation, while drugs administered im or sc need more time to reach the blood (depot effect), and consequently the pharmacokinetic (PK) profiles could be different. Besides the PK, the route of administration may have influence on the primary distribution of the drug. For example, when administered sc, smaller and hydrophiUic proteins tend to enter the venous system, while larger and/or more hydrophobic proteins tend to... 

FA consists of nondegradable mineral oil, which creates the depot effect. The complete FA also includes dead mycobacterial tuberculosis, which triggers the immune response. FA and... 

For the antigen injection, the experimenter has a choice among intramuscular (im), intra-dermal (id), subcutaneous (sc), intravenous (iv), or intraperitoneal (ip) injection. In bigger animals, with some anatomical knowledge, injection into the lymph nodes is also possible. The id injection requires skill, but it is said to give a better immune response. In addition, it provides for a longer depot effect. Chopped-up gel pieces cannot be injected intradermally and mouse skin is too thin for id injections. 

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