Depot preparation

It should be pointed out that cubic phases, such as the one discussed in this work, frequently occur in lipid-water systems (77), and the concept of using cubic phases as drug vehicles is therefore not limited to the use of monoolein only. From a toxicological stand-point, it is tempting to try to use membrane lipids, such as phospholipids, instead of monoolein for parenteral depot preparations (18-20). 

Combine it with a daily routine like when waking up, at breakfast, to the 9 o clock news etcetera. Food interactions must be considered (below) Reduce the number of daily intake. Use Depot preparations or medications with longer half-life. 

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... 

One of the main disadvantages of depot parenteral preparations is that administration of these preparations may not be acceptable to the patient. The depot preparation requires a lower dosing frequency when compared with other dosage forms. 

When esterified with a fatty acid, both fluphenazine and haloperidol can be applied intramuscularly as depot preparations. 

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... 

Huphenazine is a short acting agent. Eor the management of agitated and potentially violent patients its hydrochloride formulation is frequently used for parenteral administration. Fluphenazine decanoate is a widely used depot preparation. Although its principal pharmacological activities are similar to those of the other phenothiazines fluphenazine displays only weak sedative action and it shows little anticholinergic and hypotensive 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. 

Used as long-acting depot preparations intramuscularly administered medroxyprogesterone acetate provides contraception for up to 3 months and norethisterone enanthate up to 2 months. These preparations can be indicated when compliance can pose problems. They are not associated with thromboembolism or cardiovascular disease. Adverse reactions are abnormal and prolonged bleeding and amenorrhoea. 

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. 

The 2004 Practice Guideline for the Treatment of Patients With Schizophrenia recommends indefinite maintenance treatment for patients who have had at least two episodes of psychosis within 5 years or who have had multiple previous episodes (Lehman et al. 2004). Maintenance therapy should involve the lowest possible doses of antipsychotic drugs, and patients should be monitored closely for symptoms of relapse. If the patient is compliant with treatment, oral medications are usually sufficient. However, if the patient s treatment history suggests that the patient may not reliably take daily oral medication, a long-acting depot preparation may be indicated. 

Lipophilic groups that are not easily hydrolyzed are used extensively for depot preparations, which liberate the active drug molecule slowly, for a period of days or weeks. Steroid hormone palmitates and pamoates, and antimalarial esters (e.g., cycloguanil pamoate, 3.29), can deliver the active drugs over a prolonged time cycloguanil, for example, is released over a period of several months. This can he a great convenience for the patient, especially in areas with remote medical facilities. 

To supplement depot medication, oral preparations can be used when early warning signals of an impending relapse occur because the pharmacokinetics of depot preparations require months to reach steady-state (see also Pharmacokinetics/Plasma Levels later in this chapter). By contrast, oral administration brings about an altered steady state in several days. We recommend treating most patients with the minimally effective dose to avoid more serious adverse effects, even at the cost of a few more relapses, provided this strategy does not lead to rehospitalization or produce serious impairment in functioning. 

Knudsen P. Chemotherapy with neuroleptics. Clinical and pharmacokinetic aspects with a particular view to depot preparations. Acta Psychiatr Scand Supp11985 322(72) 51-75. 

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. 

Women with endometriosis receive treatment courses of 6 months duration. Concomitant low-dose hormone replacement therapy has been reported to diminish bone loss without significantly decreasing clinical effectiveness. Women with uterine fibroids that are symptomatic (menorrhagia, anemia, pain) receive treatment courses of 3 months, by which time women have amenorrhea or reduced menorrhagia uterine fibroids are reduced in size an average of 37%. Intramuscular depot preparations containing 3.75 mg (monthly) or 11.5 mg (every 3 months) are used. 

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

K. Lehmann, D. Dreher, Permeable acrylic resin coatings for the manufacture of depot preparations of drugs, Drugs Made in Germany 11 34 (1968). 

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