Diffusion parenteral drugs

Intramuscular and subcutaneous injections are by far the most common means of parenteral drug administration. Because of the high tissue blood flow and the ability of the injected solution to diffuse laterally, drug absorption generally is more rapid after intramuscular than after subcutaneous injection. Drug absorption from intramuscular and subcutaneous sites depends on the quantity and composition of the connective tissue, the capillary density, and the rate of vascular perfusion of the area. These factors can be influenced by the coinjection of agents that alter local blood flow (e.g., vasoconstrictors or vasodilators) or by substances that decrease tissue resistance to lateral diffusion (e.g., hyaluronidase). 

Another facet of parenteral drug delivery is the implanted device, and this is perhaps the most promising and most readily commercialised area for responsive and/or active polymers. For an implanted vehicle or depot, drag release rate is controlled by dissolution and/or diffusion in the formulation, or for solid polymer implants by diffusion and/or degradation of the polymer. For more complex polymer hydrogels, the release can be controlled by the linking chemistries, and these can be made responsive to a wide variety of stimuli such as enzymatic action, redox potential and so on, as well as those noted above for the oral route. 

Significant differences in the extent of distribution of drugs, particularly lipid-soluble organic bases, are usual between ruminant and monogastric species. After parenteral administration, lipophilic bases diffuse passively from the systemic circulation into ruminal fluid (pH 5.5-6.5), where they become trapped by ionization. These drugs are slowly reabsorbed or, if they possess fimctional groups suitable for metabolism by hydrolysis or reduction, they may be partially inactivated by ruminal micro-organisms. 

The United States Food and Drug Administration issued a safety alert in 1994 regarding the potentially life-threatening formation of precipitates in parenteral nutrition admixtures (148). They had received reports of two deaths and at least two cases of respiratory distress during intravenous infusion of a three-in-one parenteral nutrition mixture (amino acids, carbohydrates, lipids). The mixture contained 10% FreAmine III (amino acids -I- magnesium acetate -I- phosphoric acid -I- potassium chloride -I- sodium acetate -I- sodium chloride), dextrose, calcium gluconate, potassium phosphate, other minerals, and a lipid emulsion. The solution may have contained a precipitate of calcium phosphate. Autopsies revealed diffuse microvascular pulmonary emboli containing calcium phosphate. 

ABSORPTION, DISTRIBUTION, AND EXCRETION Isoniazid is readily absorbed after oral or parenteral administration. Isoniazid diffuses readily into aU body fluids and cells. The drug achieves significant quantities in pleural and ascitic fluids concentrations in the cerebrospinal fluid (CSF) with inflamed meninges are similar to those in the plasma. Isoniazid penetrates well into caseous material and persists in therapeutic concentrations. 

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