Blood circulation administration route

DTPA-SWNTs or DTPA-MWNTs labelled with111 In (0.06 or 0.4mg/ mouse) Female BALB/c mice Intravenous administration 30 min, 3h, and No toxic side effects, accumulation, or 24 h mortalities were observed. CNTs were removed from systemic blood circulation though the renal excretion route Singh et al. (2006)... 

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... 

Parenteral (injected) administration of drugs provides a solution to many problems associated with the oral delivery route. A drug injected into the blood circulation is considered to be completely bioavail-able thaefore, the quantity of the surfactants and otha inactive excipients in intravenous dosage forms are usually strictly limited. The most common alternative routes of parenteral drug administration are intramuscular or subcutaneous injections [2], Several otha injection routes are available to elicit rapid local reaction, such as intrathecal, intraarticular, and intracardiac. 

Often, the active substance is released from its administration form in a dissolved state. If this is not the case, the active substance must first dissolve in aqueous environment after it has been released. Only in the dissolved state, can an active substance pass biological membranes separating the site of administration from the systemic circulation (the blood circulation) via which transport to the site of action occurs. The fraction of the administered active substance that dissolves in the aqueous fluid adjacent to the biological membranes and thereby becomes available for passing them is called the pharmaceutical availability. The fraction of the total amount of the administered active substance that ultimately reaches the systemic circulation in an unchanged form is called bioavailability. By definition, an intravenously injected medicine will have a bioavailability of 1.0 (or 100 %). When a medicine is administered via a different route, its bioavailability will be reduced, due to, for example, incomplete dissolution or losses during the transport of dissolved active substance to the systemic circulation. 

An active substance generally exerts its effect through defined molecular interactions with a receptor. As a prerequisite, the substance needs to be dissolved and reach the receptor. For a local effect, the substance is usually administered in close proximity to the desired target and should penetrate into body tissues as little as possible. However, when a systemic effect is desired, the substance has to reach the blood circulation system for distribution. For extravascular administration routes, this requires membrane passage and may expose the substance to various pre systemic elimination mechanisms, including metabolism and efflux transporters such as P-glycoprotein. 

The definition of bioavailability given above includes elements of the rate of drug entry into the target compartment as well as the total amount. Let us assume that the blood circulation is the target compartment and that i.v. administration is the standard route to which all others must be compared. Then F may be calculated as the ratio of the area under the plasma concentration versus time curve of the test drug (or route) to that of the standard when equal doses are administered ... 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

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