Insuhn lispro

Insuhn lispro injection (rDNA origin) [FDA] Humalog Mix75/25 [TR]... 

A 43-year-old man with type 1 diabetes developed local pruritus, redness, and swelling 4—5 times a week, 15-20 minutes after an injection, subsiding within 1-2 hours (132). Later he had a generalized urticarial reaction 5 minutes after an injection. Insuhn lispro did not help. When checked for allergens, he was positive for all types of insulin and negative for additives. With oral mizolastine the local reactions abated for a week, but then reappeared with every injection. Generalized urticaria recurred later. With continuous subcutaneous insulin infusion the local reactions immediately disappeared and metabolic control was improved. 

Lepore M, PampaneUi S, FaneUi C, PorceUati F, Bartocci L, Di Vincenzo A, Cordon C, Costa E, Brunetti P, Bolh GB. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insuhn analogue glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insuhn lispro. Diabetes 2000 49(12) 2142-8. 

Rave K, Heinemann L, Puhl L, Gudat U, Woodworth JR, Weyer C, Heise T. Premixed formulations of insuhn lispro. Activity profiles in type 1 diabetic patients. Diabetes Care 1999 22(5) 865-6. 

Hedman CA, Lindstrom T, Arnqvist HJ. Direct comparison of insuhn lispro and aspart shows smah differences in plasma insuhn profiles after subcutaneous iujectiou iu type 1 diabetes. Diabetes Care 2001 24(6) 1120-1. 

Insulin delivery by a pump may be superior to glargine insuhn. Continuous subcutaneous insulin infusion was compared with intensive therapy with insulin glargine plus insulin lispro in 19 patients (170). The patients who received insuhn glargine were exposed to glucose concentrations under 3.9 mmol/1 overnight for three times as long as those who used continuous subcutaneous insuhn infusion. 

The new, short-acting insulins can be bound to protamine, allowing the preparation of mixed formulations. In an open, randomized, single-dose, three-way, crossover trial biphasic insuhn aspart 30 (30% aspart plus 70% protaminated aspart, BIAsp 30), biphasic insulin lispro 25 (25% hspro plus 75% protaminated lispro. Mix 25), and biphasic human insulin 30 (30% regular plus 70% isophane insuhn, BHI 30) were compared in 45 patients (15). Biphasic insulin aspart improved postprandial control better. There were 23 episodes of hypoglycemia with BIAsp 30, 19 with Mix 25, and 11 with BHI 30 two episodes with BIAsp 30, five with Mix 25, and two with BHI 30 required third-party intervention. 

In 619 patients with type 1 diabetes treated with protamine zinc insulin and insulin lispro, randomized to once-daily insuhn glargine or to once-daily or twice-daily protamine zinc insulin for 16 weeks in an open study, there was no difference in the frequency of hjrpoglycemic episodes, severe hjrpoglycemia, or HbAic (21). Fasting plasma glucose concentrations were lower with insulin glargine. 

InsuUn lispro induces more rapid and constant release of insulin from the injection site, since it consists of monomeric insulin. The change of one or more amino acids in the insulin molecule prevents insuhn from forming dimers or hexamers. More rapid absorption, rapid availability, and rapid inactivation make the action better than that of endogenously secreted insuhn. When the interval between meals is long, the premeal blood glucose concentration increases rapidly. 

The new short-acting insulins can be bound to protamine, allowing the preparation of mixed formulations. In a randomized, open, crossover study for 24 weeks, a 50% mixture of insulin lispro and protamine lispro injected immediately before each meal plus NPH in the evening gave a comparable profile to regular insuhn injected 30 minutes before each meal plus NPH in the evening (7). There were no differences in HbAic or... 

When insulin lispro and insuhn aspart were compared in a single-blind, randomized crossover study in 14 patients with type 1 diabetes, insulin lispro had a faster onset of action but a shorter duration (22). However, in another study, the pharmacokinetic and pharmacodynamic profiles of insulin aspart compared with human insulin in 24 healthy Japanese were the same as those in non-Japanese subjects (23). 

Ampudia-Blasco FJ, Hasbum B, Carmena R. A new case of lipoatrophy with lispro insulin in insuhn pump therapy is there any insulin preparation free of complications Diabetes Care 2003 26(3) 953. ... 

Rapid-acting (regular or Lispro (Humalog) insuhn) Onset 1/2 to 1 hour, peak 2 to 4 hours, and duration of 6 to 8 hours... 

IV injection is short, and changes in TV insulin rates whl reach steady state in approximately 45 minutes. Intravenous pharmacokinetics of other soluble insulins (lispro, aspart, glulisine, and even glargine) appear similar to TV regular insulin, but they have no advantages over IV regular insuhn and are more expensive. 

The two forms of lipodystrophy, though less common today in people with diabetes, still occur. Lipohypertrophy is caused by many injections into the same injection site. Due to insulin s anabolic actions, a raised fat mass is present at the injection site with resultant variable insulin absorption. Lipoatrophy, in contrast, is thought to be due to insulin antibodies, with destruction of fat at the site of injection. Injection away from the site with more purified insuhn is recommended, though several reports of lipoatrophy with lispro have been reported. 

Human insulin is derived from a biosynthetic proems using strains of Escherichia coli (recombinant DNA, rDNA). Human insulin )pears to cause fewer allergic reactions than does insulin obtained from animal sources. Insuhn analog, insulin lispro, and insuhn aspart are newer fomis of human insulin made by using recombinant DNA technology and are structurally similar to human insulin. 

Fig. 1. Trends in the use of insuhn in Denmark in the new millennium, all insuhns (defined daily doses, DDD) (A), fast-acting insuhns (left human insuhn, middle lispro, right aspart) (B), basal insuhns (left glargine, middle detemir, right human insuhn) (C). (From The Danish Medicines Agency at www.dkma.dk.) The numbers reflect the use of insuhn in 44,467 patients in 2001, increasing to 56,501 in 2005. Total use of analogues is increasing.

Figure 5.5 Primary structures of (a) human insulin (mol wtmonoisotopic = 5803.6 Da), (b) Humalog LisPro (mol wt, onoisotopic = 5803.6 Da), (c) Novolog Aspart (mol wt ono otopic = 5821.6Da), (d) Glulisine Apidra (mol whnonoisotopic = 5818.6Da), (e) Lantus Glargine (mol wtmonoisotopic = 6058.8Da), and (f) Detemir (mol wtmonoisoiopic = 5913.8Da). Disulfide bonds are indicated in case of human insuhn (a) only but are present in all synthetic derivatives.

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