Depot preparations/injections

Although the time to peak drug concentration is often on the order of 1 to 2 h, depot preparations given by IM injection are absorbed extremely slowly. Numerous... 

Many drugs are administered as parenterals for speed of action because the patient is unable to take oral medication or because the drug is a macromolecule such as a protein that is unable to be orally absorbed intact due to stability and permeability issues. The U.S. Pharmacopoeia defines parenteral articles as preparations intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal. They include intravenous, intramuscular, or subcutaneous injections. Intravenous injections are classified as small volume (<100 mL per container) or large volume (>100 mL per container) injections. The majority of parenteral dosage forms are supplied as ready-to-use solutions or reconstituted into solutions prior to administration. Suspension formulations may also be used,101 although their use is more limited to a subcutaneous (i.e., Novolin Penfill NOVO Nordisk) or intramuscular (i.e., Sandostatin LAR Depot Novartis) injection. Intravenous use of disperse systems is possible but limited (i.e., Doxil Injection Ortho Biotec). 

Estrogen preparations. Depot preparations for i.m. injection are oily solutions of esters of estradiol (3- or 17-OH group). The hydrophobicity of the acyl moiety determines the rate of absorption, hence the duration of effect... 

Betamethasone is hardly ever used orally. It has a long duration of activity and can therefore also be used for alternate-day therapy. The parenteral formulation is also the sodium phosphate salt which when given IV or IM has a rapid onset of action. There are many similarities with dexamethasone such as their metabolic pathways and the indications for which both steroids are used, like the prevention of neonatal RDS and reduction of raised intracranial pressure. Combinations of betamethasone acetate and sodium phosphate have, when used for intra-articular and intra-lesional injections, the dual advantage of a rapid onset of action together with the long duration of action of a depot preparation. 

For patients with chronic psychotic symptoms who do not comply with a daily medication regimen, a long-acting depot preparation should be considered after stabilization with oral medication. Fluphenazine, haloperidol, and risperidone are the only long-acting injectable antipsychotic medications currently available in the United States. 

Treatment can be carried out with injections of leuprolide or nasal application of nafarelin. Leuprolide treatment is usually initiated at a dosage of 0.05 mg/kg body weight injected subcutaneously daily and then adjusted on the basis of the clinical response. Pediatric depot preparations of leuprolide are also available. The recommended initial dosage of nafarelin for central precocious puberty is 1.6 mg/d. This is achieved with two-unit dose sprays (each spray contains 0.1 mL, 0.2 mg) into each nostril twice daily. Treatment with a GnRH agonist is generally continued to age 11 in females and age 12 in males. 

The toxicity of therapeutic doses of ACTH resembles that of the glucocorticoids (see Chapter 39 Adrenocorticosteroids Adrenocortical Antagonists), with the added adverse effect of hyperandrogenism in women. The occasional development of antibodies to animal ACTH or to depot cosyntropin (a preparation not currently available in the USA) has produced anaphylactic reactions or refractoriness to ACTH therapy in a few individuals. Painful swelling occurs at the injection site more often with the zinc hydroxide depot preparation than with the gelatin preparation. Contraindications are similar to those of glucocorticoids. When immediate effects are desired, glucocorticoids are preferable. 

Leuprolide is available in solution for daily subcutaneous injection and in slow-release depot preparations in which leuprolide is lyophilized in microspheres given by intramuscular injection. 

Cetrorelix has been given in doses of 3 mg by subcutaneous injection of a depot preparation once weekly for 8 weeks. 

The most important action is to ensure that the client receives appropriate pharmacological treatment. One of the main problems in schizophrenia is lack of medication compliance. This is often caused by lack of client collaboration, often explained by the intrinsic pathological characteristics of the disease itself. Both typical and atypical depot antipsychotics formulations are available. Depot preparations are typically administered by intramuscular injection every 1-4 weeks. This may be of great advantage in patients with poor compliance. 

Advantages are that the route is reliable, suitable for irritant dmgs, and depot preparations (neuroleptics, hormonal contraceptives) can be used at monthly or longer intervals. Absorption is more rapid than following subcutaneous injection (soluble preparations are absorbed within 10-30 min). 

Knowledge of depot preparations (long-acting, injectable medications) also can be invaluable when working with chronic clients who need long-term therapy or who are difficult in terms of compliance (Lehne Scott, 1996). 

The more recent development of a slow-release (depot) formulation of goserelin [81 ] has allowed the administration of the agonist as a single monthly injection. Such a depot preparation has obvious clinical advantages. The peptide was incorporated in a 50 50 lactide-glycolide copolymer in the form of a small cylindrical rod, which can be injected, under local anaesthesia, through a 16-gauge needle, into the subcutaneous tissue of the anterior abdominal wall. 

Ininiiniiscular and subcutaneous injections. Drugs in aqueous solution arc usually absorbed fairly rapidly, but absmption can be slowed by giving the drug in the form of an e.ster(e.g. neuroleptic depot preparations. Chapter 27). 

Insulin, whatever its source, may be formulated in a number of ways. This directly affects its activity profile upon administration to diabetic patients. Fast (short)-acting insulins are those preparations that yield an elevated blood insulin concentration relatively quickly after their administration, which is usually by s.c. or, less commonly, by i.m. injection. Slow-acting insulins, on the other hand, enter the circulation much more slowly from the depot (injection) site. This is characterized by a slower onset of action, but one of longer duration (Table 8.4). 

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