Therapeutic injections injection products

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). 

Several other events occur simultaneously with these activities. Some events focus on extending therapeutic applications and formulations. Clinical studies are conducted to extend the diseases (indications) for which the drug is proven efficacious and safe. For example, TAXOL was initially approved for the treatment of ovarian cancer, and was later extended for the treatment of breast cancer after follow-on clinical studies demonstrated efficacy for the new indication. In addition, new product formulations are investigated to extend the routes of administration for patient convenience, increased bioavailability, and new disease therapies. For example, a drug initially developed as an injectable product may be formulated as a tablet for oral administration. 

The growth of testosterone-dependent tumors can be blocked by long-term administration of the three LH-RH analogs. The first therapeutic application of 32, 33, and 34 was in the treatment of prostate carcinomas. Buserelin came on the market as a nasal spray (Suprefact , 32) and leuprorelin (Carcinil , 33) as an injectable product in 1984. 

Therapeutic peptides and proteins are far more stable in the solid state compared to the liquid state. Delicate proteins often significantly degrade within hours when held at room temperature in the liquid state. All FDA approved therapeutic proteins for human use are injectable products, except Exubera the first inhaleable insulin. A recent survey has shown that 12 of the 30 commercial products are available only as dry powder and 28 of the 30 require refrigeration (49). Not having to refrigerate a pharmaceutical product greatly increases convenience and significantly reduces transportation and distribution costs, this is particularly true for vaccines, where an alternative to break the so called distribution cold chain is badly needed in third world countries. 

Some of the key factors in considering specific delivery systems are safety, stability, and efficacy. The parenteral administration of proteins and peptides today offers assured levels of bioavailability and the ability of the product to reach the marketplace first. It is safe to assume that over 95% of the protein therapeutics approved by the Food and Drug Administration (FDA) today are injectable products since parenteral administration avoids physical and enzymatic degradation. 

Toxicity from local anesthetics (other than cocaine) is usually caused by therapeutic overdosage (ie, excessive doses for local nerve blocks), inadvertent acceleration of intravenous infusions (lidocaine), or accidental injection of products meant for dilution (eg, 20% lidocaine) instead of those formulated for direct administration (2% solution). Acute injection of lidocaine has also been used as a method of homicide. 

The fact that ceU culture-derived products are often injected into humans as therapeutic agents makes it imperative that there be no component in the final product that can pose a potential health risk to the patient. Health risks can be introduced into a product from many sources including the ceUs themselves raw materials, such as semm, media components, etc materials used in purification, eg, antibodies and external contamination. Eor a therapeutic product such risk factors are identified at the outset and ways of reducing them to acceptable levels are designed into the process. Before a product is released by the EDA the manufacturer has to demonstrate this risk reduction by rigorous validation of the process. 

For a number of liposome preparations—both injectables and locally administered products—the therapeutic advantages over existing formulations have been proven in animal models clinical trials with liposome preparations are now under way. So far, clinical studies showed no significant toxic effects which could be ascribed to the lipid components of the liposomes used. 

Levothyroxine (Synthroid , Levoxyl , Unithroid ), other brands, and generics Synthetic LT4 25, 50, 75, 88, 100, 112, 125, 137, 150, 1 75, 200, and 300 meg tablets 500 meg vial for injection 60 meg Gold standard for treating hypothyroidism products not therapeutically equivalent full replacement dose 1-1.6 meg/kg per day when switching from animal product, lower calculated daily dose by 25-50 meg intravenous form rarely needed... 

For this calculation, it is unnecessary to assume that Vd and/or kei are the same for the two studies. It is only necessary that fe be the same in both studies. This is usually a valid assumption unless the drug undergoes a significant amount of first-pass metabolism in the gut wall or liver following oral administration or a significant amount of decomposition at an intra muscular (IM) injection site. When this occurs, the availability of the extravascular dosage form may appear to be low, but the fault will not lie with the formulation. The bioavailability will be a true reflection of the therapeutic efficacy of the drug product, and reformulation may not increase bioavailability. 

Very few injectable dosage forms have been specifically developed and approved by FDA for intraocular use. However, the ophthalmologist uses available parenteral dosage forms to deliver antiinfectives, corti-costerioids, and anesthetic products to achieve higher therapeutic concentrations intraocularly than can ordinarily be achieved by topical or systemic administration. These unapproved or off-label uses have developed over time as part of the physician s practice of medicine. However, these drugs are usually administered by subconjunctival or retrobulbar injection and rarely are they injected directly in the eye [301]. 

As pharmaceutical scientists gain experience and tackle the primary challenges of developing stable parenteral formulations of proteins, the horizons continue to expand and novel delivery systems and alternative routes of administration are being sought. The interest in protein drug delivery is reflected by the wealth of literature that covers this topic [150-154]. Typically, protein therapeutics are prepared as sterile products for parenteral administration, but in the past several years, there has been increased interest in pulmonary, oral, transdermal, and controlled-release injectable formulations and many advances have been made. Some of the more promising recent developments are summarized in this section. 

If we are to harness the placebo effect and make use of it in clinical practice, we first have to understand how it works. A number of factors have been proposed as explanations of the placebo effect. These include the relationship between doctors and patients, the patient s beliefs and expectations, the production of opiates in the brain, and a phenomenon called classical conditioning, in which people come to associate pills and injections with therapeutic effects, just as Pavlov s dogs came to associate the sound of a bell with the presentation of food. In this chapter we look at how all of these processes combine to produce placebo effects, and we consider their implications for the treatment of depression. 

Fourth, we are interested in information on the various presentations of each product. The presentations differ in pharmaceutical form (tablets, capsules, injectables, creams and so on), the concentration of the therapeutic active ingredient (usually specified in milligrams) and the number of tablets, vials, or units in general, provided in each package. The Spanish data enable us to identify the number of units per package for all the observations. The... 

Absorption/Distrlbutlon - Phenytoin is slowly absorbed from the small intestine. Rate and extent of absorption varies and is dependent on the product formulation. Bioavailability may differ among products of different manufacturers. Administration IM results in precipitation of phenytoin at the injection site, resulting in slow and erratic absorption, which may continue for up to 5 days or more. Plasma protein binding is 87% to 93% and is lower in uremic patients and neonates. Volume of distribution averages 0.6 L/kg. Phenytoin s therapeutic plasma concentration is 10 to 20 mcg/mL, although many patients achieve complete seizure control at lower serum concentrations. 

Insulin preparations used initially were little more than crude pancreatic extracts. The therapeutic value of such products was marginal, as severe adverse reactions were commonplace (due to the presence of impurities). This was made worse by the frequency of injections required. The introduction of an acid-alcohol precipitation step yielded insulin preparations of moderate purity, thus partially overcoming the range and severity of side effects noted. 

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