Apidra

Apidra is a brand name for insulin glulisine, a fast-acting human analog manufactured by Aventis. It is a soluble insulin and can be used intravenously for diabetic emergencies such as DKA. Apidra has been found to be equipotent (equally potent) to R/neutral R-DNA/GE/GM insulin when administered intravenously.

Given subcutaneously in normal injection form, Apidra has a more rapid onset and shorter duration than R human insulin.

Technical details

Insulin hexamers must break down into dimers and monomers to be absorbed. .

Alterations in the human insulin chains to produce Apidra (Glulisine), Novolog/NovoRapid (Aspart), and Humalog (Lispro)--all rapid-acting analog insulins.

The alterations to the human insulin molecule that produces insulin Glulisine are all to the B insulin chain; position B-#3, which is normally amino acid asparagine is replaced with lysine and the lysine amino acid which is normally found at position B-#29 is replaced by glutamic acid. . Making substitutions at these positions on the B insulin chain, inhibits hexamer formation

Since insulin in hexamer form must break down into dimers and monomers to become active, inhibiting the molecule's natural tendency to form hexamers by self-association, means better, faster absorption, more rapid onset, peak and shorter duration. Apidra may be diluted for all uses except in insulin pumps. It may be mixed in the same syringe with NPH/isophane insulin only.

There is no clinical data regarding same syringe mixing of Apidra and any other insulin preparations in humans, but testing conducted in dogs indicates a slower onset when mixed with NPH/isophane insulin. Used on its own, Apidra displayed an earlier onset with them. Antibody formation in the dog was noted.

Dr. Nelson of University of California-Davis said in his lecture at the Ohio State Endocrinology Symposium in 2006 that if the short-acting analog insulins have any role in feline and canine diabetes, it is not yet determined.

Fast Acting Insulins
	All analogs. All soluble.
NovoRapid-insulin Aspart
Apidra-insulin Glulisine
Humalog-insulin Lispro

Analog Insulins: amino acid sequences

Amino Acid Sequence of Insulin Preparations
Amino Acid Substitutions
	A-Chain Position			B-Chain Position
Source Species	A-8	A-10	A-21	B-28	B-29	B-30	B-31 B-32
Beef	Ala	Val	Asn	Pro	Lys	Ala	N/A
Pork	Thr	Ilc	Asn	Pro	Lys	Ala	N/A
Human	Thr	Ilc	Asn	Pro	Lys	Thr	N/A
Aspart (Novolog)	Thr	Ilc	Asn	Aspartic Acid	Lys	Thr	N/A
Lispro (Humalog)	Thr	Ilc	Asn	Lys	Pro	Thr	N/A
Glulisine (Apidra)	Thr	Ilc	Asn	Pro	Glu	Thr	N/A
Lantus (glargine)	Thr	Ilc	Gly	Pro	Lys	Thr	Arg
Levemir(detemir)	Thr	Ilc	Asn	Pro	Lys	N/A	Myristic Acid
Ala=Alanine Val=Valine Asn=Asparagine Pro-Proline Lys=Lysine Thr=Threonine Ilc=Isoleucine Glu-Glutamine Gly=Glycine

Analog Insulins: pharmacokinetics

Pharmacokinetics of Insulin Preparations
Insulin Preparations	Onset (hr)	Peak (hr)	Duration (hr)
Rapid-Acting
R/Neutral	0.5 to 1	2.5 to 5	8 to 12
Lispro (Humalog)	0.25 to 0.5	0.5 to 1.5	2 to 5
Aspart (Novolog)	0.17 to 0.33	1 to 3	3 to 5
Glulisine (Apidra)	0.17 to 0.33	1 to 3	3 to 5
Intermediate-Acting
NPH Isophane	1 to 1.5	6 to 14	16 to 24
Lente	1 to 3	6 to 14	20+
70/30-30/70	0.5 to 1	2 to 12	24
50/50	0.5 to 1	2 to 12	24
Novolog 70/30 Mix	0.25	1 to 3	24
Humalog 75/25 Mix	0.25	0.5 to 1.5	24
Long-Acting
Ultralente	6	14 to 18	18 to 24
PZI	4 to 6	14 to 18	24 to 36
Glargine (Lantus)	1.1	N/A	24
Detemir (Levemir)	0.8 to 2	N/A	24

These are human activity profiles.