Intramuscularly

The development of freeze-drying for the production of blood derivatives was pioneered during World War II (96,97). It is used for the stabilization of coagulation factor (98,99) and intravenous immunoglobulin (IgG iv) products, and also for the removal of ethanol from intramuscular immunoglobulin (IgG im) solutions prior to their final formulation (Fig. 2). 

The resuspended and formulated Fraction II precipitate normally contains some aggregated IgG and trace substances that can cause hypotensive reactions in patients, such as the enzyme prekail ikrein activator (186). These features restrict this type of product to intramuscular adininistration. Further processing is required if products suitable for intravenous adininistration are required. Processes used for this purpose include treatment at pH 4 with the enzyme pepsin [9001-75-6] being added if necessary (131,184), or further purification by ion-exchange chromatography (44). These and other methods have been fiiUy reviewed (45,185,187,188). Intravenous immunoglobulin products are usually suppHed in the freeze-dried state but a product stable in the solution state is also available (189). 

Vasopressin is suppHed as Pitressin Taimate (Parke-Davis) for use as an antidiuretic agent adrninistered intramuscularly (see Diuretic agents). 

Pituitary Dwarfism. Pituitary dwarfism is a condition characterized by an inabiHty to produce or secrete normal levels of endogenous hGH. The condition results in reduced heights of individuals afflicted with the condition and has been treated by intramuscular or subcutaneous injection of hGH. Pituitary hGH was used prior to the approval of biosynthetic hGH. If treatment is initiated early enough, the patient can attain a final adult height weU within the normal range. 

Progesterone. Progesterone (1) is not orally active. Although seldom used clinically, it can be adrninistered as an intramuscular injection, pessaries, or suppositories in the treatment of menstmal disorders and habitual abortion (121). Progesterone can be recrystaUized from dilute alcohol and exists in two crystalline forms (122). It is soluble in chloroform and ethanol sparingly soluble in acetone, dioxane, ether, and fixed oils and practically insoluble in water (121). Two syntheses of progesterone (1) are described in Figure 3. 

Intravenous aqueous injections provide an excellent means of achieving a rapid therapeutic response. Parenteral product design, eg, vehicle and other excipient selection, as well as choice of route of adrninistration, can prolong therapeutic activity and increase onset times. Thus, oily solutions, suspensions, or emulsions can be adrninistered by subcutaneous or intramuscular routes to create prolonged effect, ie, depot injection (28). 

Prolonged Action Parenterals Injections. Intramuscular injections have been developed to achieve prolonged therapeutic effects. This can be accompHshed by suspension of dmg particles in oils or flowable gels, from which the dmg slowly diffuses. Aqueous suspensions can also provide such therapeutic response. In these cases, the soHd dmg crystals generally are quite water insoluble and of a controlled particle size and crystallized form. 

Florfenicol concentrations in tissues and body fluids of male veal calves were studied after 11 mg/kg intramuscular doses adininistered at 12-h intervals (42). Concentrations of florfenicol in the lungs, heart, skeletal muscle, synovia, spleen, pancreas, large intestine, and small intestine were similar to the corresponding semm concentrations indicating excellent penetration of florfenicol into these tissues. Because the florfenicol concentration in these tissues decreased over time as did the corresponding semm concentrations, it was deemed that florfenicol equiUbrated rapidly between these tissues and the blood. Thus semm concentrations of florfenicol can be used as an indicator of dmg concentrations in these tissues. 

Manufacture of vitamin C starts with the conversion of sorbitol to L-sorbose. Sorbitol and xyHtol have been used for parenteral nutrition following severe injury, bums, or surgery (246). An iron—sorbitol—citric acid complex is an intramuscular bematinic (247). Mannitol administered intravenously (248) and isosorbide administered orally (249) are osmotic diuretics. Mannitol hexanitrate and isosorbide dinitrate are antianginal dmgs (see Cardiovascular agents). 

The relative toxicities of thallium compounds depend on their solubHities and valence states. Soluble univalent thallium compounds, eg, thaHous sulfate, acetate, and carbonate, are especiaHy toxic. They are rapidly and completely absorbed from the gastrointestinal tract, skin peritoneal cavity, and sites of subcutaneous and intramuscular injection. Tb allium is also rapidly absorbed from the mucous membranes of the respiratory tract, mouth, and lungs foHowing inhalation of soluble thallium salts. Insoluble compounds, eg, thaHous sulfide and iodide, are poorly absorbed by any route and are less toxic. 

Calcitonin. Calcitonin is available commercially from pork and salmon extracts (Calcimar, Armour) as well as by synthesis. Preparations are bioassayed on the basis of their calcium-lowering activity in comparison to the potency of pure pork calcitonin of which ca 4 p.g is equivalent to 1 MRC unit (Medical Research Council, U.K.). For clinical use, vials containing 400 units in 4 mL are available. The recommended daily dosage is 100 units to be adrninistered subcutaneously or intramuscularly because its plasma half-life is short (4—12 min). 

In order to induce a toxic effect, local or systemic, the causative material must first come into contact with an exposed body surface these are the routes of exposure. In normal circumstances, and depending on the nature of the material, the practical routes of exposure are by swallowing, inhalation, and skin and eye contact. In addition, and for therapeutic purposes, it may be necessary to consider intramuscular, intravenous, and subcutaneous injections as routes of adininistration. 

Dietary deficiency in the absence of absorption defects can be effectively reversed with oral supplementation of 1 p.m of vitamin B 2 daily. If deficiency is related to a defect in vitamin absorption, daily doses of 1 pg adininistered subcutaneously or intramuscularly are effective (33). However, a single intramuscular dose of 100 pg of cobalamin once per month is adequate in patients with chronic gastric or ileal damage. Larger doses are generally rapidly cleared from the plasma into the urine and are not effective unless the patient demonstrates poor vitamin retention. 

Cobalamin should be adininistered parenteraHy by the intramuscular or subcutaneous route. Isolated cases of anaphylaxis have been reported with intravenous administration. 

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

Newer bleomycins such as peplomycin and especially liblomycin, are more resistant to bleomycin hydrolase. This results in less lung toxicity but more bone marrow toxicity, and allows for a different spectmm of antitumor action. Bleomycin is inactive orally it is given intravenously, intramuscularly, subcutaneously, or directiy into a cavity such as the pleural cavity. The majority of dmg is excreted unchanged in the urine. 

Meglumine [6284-40-8] antimonate [133-51 -7] C H NO HO Sb, (Glucantime) is a pentavalent antimonial used for the treatment of leishmania sis in Latin America (207) and in the French-speaking areas of Europe and Africa (206). It is adrxiinistered by deep intramuscular injection. Although relatively safe and usually well tolerated, numerous side effects have been observed. It is not available in the United States. 

Melarsonyl potassium (Mel W, Trimelarsen) [13355-00-5] is a thioarsenite closely related to melarsoprol, and it also has been used for the treatment of trypanosomiasis (172). However, it appears to be more toxic and less effective than melarsoprol. The only advantage of melarsonyl potassium is that it is water-soluble and can be adrninistered intramuscularly or subcutaneously. This property is useful when the intravenous route caimot be employed. 

Procainamide may be adininistered by iv, intramuscular (im), or po routes. After po dosing, 75—90% of the dmg is absorbed from the GI tract. About 25% of the amount absorbed undergoes first-pass metaboHsm in the fiver. The primary metabolite is A/-acetylprocainamide (NAPA) which has almost the same antiarrhythmic activity as procainamide. This is significant because the plasma concentration of NAPA relative to that of procainamide is 0.5—2.5. In terms of dmg metabolism there are two groups of patients those that rapidly acetylate and those that slowly acetylate procainamide. About 15—20% of the dmg is bound to plasma proteins. Peak plasma concentrations are achieved in 60—90 min. Therapeutic plasma concentrations are 4—10 lg/mL. Plasma half-lives of procainamide and NAPA, which are excreted mainly by the kidneys, are 2.5—4.5 and 6 h, respectively. About 50—60% is excreted as unchanged procainamide (1,2). 

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