Page 768 - Basic _ Clinical Pharmacology ( PDFDrive )

754 SECTION VII Endocrine Drugs

TABLE 41–6 Some insulin preparations available in the United States. 1

Preparation Species Source Concentration
Short-acting insulins
Insulin lispro (Humalog, Lilly) Human analog U100, U200
Insulin aspart (Novolog, Novo Nordisk) Human analog U100
Insulin glulisine (Apidra, Sanofi Aventis) Human analog U100
Regular insulin (Humulin R, Lilly; Novolin R, Novo Nordisk) Human U100, U500
Regular insulin inhaled (MannKind) Human —
Long-acting insulins
NPH insulin (Humulin N, Lilly, Novolin N, Novo Nordisk) Human U100
Insulin glargine (Lantus, Toujeo, Sanofi Aventis, Basaglar, Lilly) Human analog U100, U300
Insulin detemir (Levemir, Novo Nordisk) Human analog U100
Insulin degludec (Tresiba, Novo Nordisk) Human analog U100, U200
Premixed insulins
70 NPH/30 regular (Novolin, Novo Nordisk; Humulin, Lilly) Human U100
75/25 NPL, Lispro (Humalog mix 75/25, Lilly) Human analog U100
50/50 NPL, Lispro (Humalog mix 50/50, Lilly) Human analog U100
70/30 NPA, Aspart (Novolog mix 70/30, Novo Nordisk) Human analog U100
70/30 Degludec/Aspart (Ryzodeg, Novo Nordisk) Human analog U100
All insulins are now made by recombinant technology; they should be refrigerated and brought to room temperature just before injection.
NPA, neutral protamine aspart; NPL, neutral protamine lispro.

The physician should then carefully note dosages in both units great convenience by patients with diabetes who object to wait-
and volume to avoid overdosage. The disposable pen avoids this ing as long as 45 minutes after injecting regular human insulin
conversion issue and dispenses the regular U500 insulin in 5-unit before they can begin their meal, patients must be taught to ingest
increments. adequate absorbable carbohydrate early in the meal to avoid hypo-
Intravenous infusions of regular insulin are particularly useful glycemia during the meal. The analogs also have lowest variability
in the treatment of diabetic ketoacidosis and during the periopera- of absorption: approximately 5%. This compares with 25% for
tive management of insulin-requiring diabetics. regular insulin. Another desirable feature of rapidly acting insulin
analogs is that their duration of action remains at about 4 hours
2. Rapidly acting insulin analogs—Insulin lispro (Huma- for most commonly used dosages. This contrasts with regular
log) is an insulin analog in which the proline at position B28 is insulin, whose duration of action is significantly prolonged when
reversed with the lysine at B29. Insulin aspart (Novolog) is a single larger doses are used.
substitution of proline by aspartic acid at position B28. Insulin The rapidly acting analogs are commonly used in insulin
glulisine (Apidra) differs from human insulin in that the amino pumps. In a double-blind crossover study comparing insulin lis-
acid asparagine at position B3 is replaced by lysine and the lysine pro with regular insulin in insulin pumps, persons using insulin
in position B29 by glutamic acid. When injected subcutaneously, lispro had lower HbA 1c values and improved postprandial glucose
these three analogs quickly dissociate into monomers and are control with the same frequency of hypoglycemia. However, the
absorbed very rapidly, reaching peak serum values in as little as concern remains that in the event of pump failure, users of the
1 hour. The amino acid changes in these analogs do not interfere rapidly acting insulin analogs will have more rapid onset of hyper-
with their binding to the insulin receptor, with the circulating glycemia and ketosis.
half-life, or with their immunogenicity, which are all identical to While insulin aspart has been approved for intravenous
those of human regular insulin. use (eg, in hyperglycemic emergencies), there is no advantage
Clinical trials have demonstrated that the optimal times in using insulin aspart over regular insulin by this route. A
of preprandial subcutaneous injection of comparable doses of U200 concentration of insulin lispro is available in a disposable
the rapid-acting insulin analogs and of regular human insulin prefilled pen. The only advantage of the U200 over the U100
are 15 minutes and 45 minutes before the meal, respectively. insulin lispro preparation is that it delivers the same dose in half
Although the more rapid onset of action has been welcomed as a the volume.