Insulin timed administration

The number and size of daily doses, time of administration, and diet and exercise require continuous medical supervision. Dosage adjustment may be necessary when changing types of insulin. Rotate administration sites to prevent lipodystrophy. Do not administer within 1 inch of the same site for 1 month. It may be best to rotate sites within an area rather than rotating areas. 

Administration of insulin—sites to be used rotation of injection sites (see Home Care Checklist Rotating Insulin Injection Sites) angle of injection administration at die time of day prescribed by the health care provider disposal of die needle and syringe... 

Intensive insulin therapy, the administration of insulin three or more times daily to maintain preprandial blood glucose levels between 70 and 120 g/dL and postprandial blood glucose levels less than 180 g/dL, has been shown to decrease the incidence of proteinuria and albuminuria in patients with diabetes, both with and without documented nephropathy. The development and progression of nephropathy is also delayed in patients with type 1 DM receiving intensive insulin therapy. Continued benefits of intensive insulin therapy have been demonstrated up to 8 years after the study.16... 

Bioavailability of human insulin assessed from pharmacological data. After extravascu-lar administration only the time course governs the observed pharmacological effects. The pharmacological data was translated into theoretical plasma-concentration data using the PK/PD model. The results of the PK/PD analysis indicate that the doses administered can be accurately predicted from pharmacological data... 

Kar S, Seto D, Dore D, Chabot J-G, Quirion R. 1997b. Systemic administration of kainic acid induces selective time-dependent decrease in [ Ijinsulin-like growth factor I, [ I] insulin-like growth factor II and [ I] insulin receptor binding sites in adult rat hippocampal formation. Neuroscience 80 1041-1055. 

INSULIN LISPRO Insulin lispro is intended for subcutaneous administration. When used as a meal-time insulin, give insulin lispro within 15 minutes before or immediately after a meal. 

INSULIN GLARGINE Give insulin glargine subcutaneously once daily at the same time every day. The dose may be administered at any time during the day. IV administration of the usual subcutaneous dose could result in severe hypoglycemia. 

Loss of blood glucose control When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur. At such times, it may be necessary to discontinue the drug and give insulin. Disulfiram-like syncframe. A sulfonylurea-induced facial flushing or breathlessness reaction may occur when some sulfonylureas are administered with alcohol. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) Water retention and dilutional hyponatremia have occurred after administration of sulfonylureas to type 2 diabetes patients, especially those with CHF or hepatic cirrhosis. 

Whenever (3-blocker therapy is employed, the period of greatest danger for asthmatics or insulin-dependent diabetics is during the initial period of drug administration, since the greatest disruption of the autonomic balance will occur at this time. If marked toxicity does not occur during this period, further doses are less likely to cause problems. 

Insulin is the protein that has been most investigated for pulmonary administration. Insulin levels are not maintained in diabetic patients, and precise control over blood glucose levels is needed. Insulin is a small protein, 5.8 kDa, which is composed of two chains that are covalently linked by an interchain disulfide bond. Currently, insulin is administered by injection, several times a day for many diabetics. The ability to deliver insulin via a noninvasive route would free diabetics from inconvenient, invasive insulin delivery methods and possibly eliminate secondary problems associated with diabetes, such as diabetic retinopathy. 

A composition based on diketopiperazine derivatives (3,6-bis (N-fumaryl-N-(n-butyl) amino-2, 5-diketopiperazine) has been investigated as a pulmonary drug delivery system, termed Technospheres (Pharmaceutical Discovery Corp., Elmsford, NY) (Pohl et al. 2000 Steiner et al. 2002). The diketopiperazine derivatives self-assemble into microparticles at low pH with a mean diameter of approximately 2 pm. During self-assembly, diketopiperazine derivatives microencapsulate peptides present in the solution. Insulin incorporated in diketopiperazine derivatives (TI) was administered to five healthy humans by the use of a capsule-based inhaler with a passive powder deagglomeration mechanism. Relative and absolute bioavailability of TI in the first 3 hours (0-180 min) were 26 12% and 15 5%, and for 6 hours (0-360 min) 16 8% and 16 6%, respectively (Steiner et al. 2002). The time to peak action for glucose infusion rates was shorter with both IV (14 6 min) injection and inhalation (39 36 min), as compared to SC administration (163 25 min). This rapid absorption of insulin would be beneficial for diabetic patients who need to rapidly affect their glucose levels. 

FIGURE 2.1 Changes in blood glucose level versus time profiles in type 1 diabetic rats following multiple oral administration of SS-ILP and subcutaneous insulin (only at the first dosing) (open square), insulin solution (open circles), and subcutaneous administration of insulin solution (closed circles). Insulin solution was used as control (open circles). The dose of insulin was 25 IU/kg (oral) and 0.1 IU/kg (subcutaneous) body weight. Each value represents mean SE (n — 5-10). Statistically significant difference from control p < 0.05 p < 0.01. (From Morishita, M. et al., J. Control. Release, 110, 587, 2006. With permission from Elsevier.)... 

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