Suspension is a part of the liquid your insulin is mixed with, to change its action profile.
The three major suspension types you'll see are Isophane, Protamine Zinc, and Zinc suspensions. Neutral insulins do not use an added suspension.
A suspension is either minerals, proteins, or both, added to the insulin's diluting liquid to slow their absorption in the body and make them work longer.[1][2].
Suspended insulins are cloudy or milky in appearance, even before they have been rolled; they must be rolled or resuspended before use or they will not be properly effective.
Analog mixed insulins are suspended by the use of protamine to create special insulin crystals. These mixes also begin with the basic insulins: Humalog, Novolog and NovoRapid.
R/Neutral insulins[]
R or neutral insulin is basically zinc insulin crystals dissolved in clear fluid with nothing added to alter its action or speed[3]--no suspension. R/Neutral insulins also have no buffer[4].
The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect[5][6], so combining them would be incompatible[7].
From 1921 to the 1930's when PZI was developed, R was the only kind of insulin available.
R/Neutral Insulins[8] | |
---|---|
All fast-acting: | |
NONE |
Isophane suspension insulins[]
NPH or isophane insulins combine protamine, zinc and insulin. The difference between NPH and its older brother, PZI, is the amount of protamine in the formula; PZI insulin has more protamine in it. The salmon-derived protamine is less readily absorbed than insulin itself; basically the system must absorb all of the protamine present in the formulation before the absorption process of the insulin can begin[9].
Mixed insulins contain a given ratio of R/Neutral and NPH/isophane insulin. These are all phosphate buffer insulins, just as NPH/isophane insulin without any addition of R/Neutral is. The phosphate buffer makes them incompatible with the Lente-type insulins for combining[10][11]. These mixed insulins are a combination of intermediate-acting NPH/isophane insulin with short-acting R/Neutral producing intermediate-acting insulins.
Isophane suspension | |
---|---|
All intermediate-acting: | |
Generic Names: |
NPH, isophane[12] Mixed insulins, biphasic[13] |
Brand Names: Non-analog, |
Actrapid, Humulin I Humulin N, Insuman Basal Insulatard, Novolin N Protaphane ReliOn/Novolin NPH |
Brand Names: Non-analog, |
Hypurin Bovine Isophane Iletin I NPH |
Brand Names: Non-analog, |
Hypurin Porcine Isophane Iletin II NPH Pork Insulatard |
Brand Names: Non-analog, |
Actraphane 20/80 Actraphane 30/70 Actraphane 50/50 Humulin 50/50, Humulin 70/30 Humulin M2, Humulin M3 Humulin M5 Insuman Comb 15 Insuman Comb 25 Insuman Comb 50, Mixtard 10 Mixtard 20, Mixtard 30 Mixtard 40, Mixtard 50 Novolin 70/30 ReliOn/Novolin 70/30 |
Brand Names: Non-analog, |
Hypurin Porcine 30/70 Mix Pork Mixtard 30 |
Generic Names: Analog Mixed |
Aspart, Lispro |
Brand Names: Analog Mixed: |
Humalog 75/25 Humalog Mix 25 Humalog 50/50 Humalog Mix 50 Novolog Mix, NovoMix 30 |
Protamine zinc suspension insulins[]
The difference between PZI and its younger brother, NPH, is the amount of protamine in the formula; PZI insulin has more protamine in it. The salmon-derived protamine is less readily absorbed than insulin itself; basically the system must absorb all of the protamine present in the formulation before the absorption process of the insulin can begin[14]. Since there's more protamine present in Protamine Zinc insulin, it takes the body longer to absorb it before going on to the absorption of the insulin itself. The longer absorption period of the extra protamine is how PZI has more duration. Both NPH/isophane and PZI insulins use phosphate buffers which makes them incompatible with the Lente-type insulins for combining[15][16].
Protamine Zinc suspension[17] | |
---|---|
All slow-acting: | |
Generic Names: |
|
Brand Names: Bovine/Porcine: |
|
Brand Names: Bovine: |
BCP PZI |
Zinc suspension insulins[]
The Lente family of insulins consist of insulin crystals of basically two different sizes--the larger ultralente and the smaller semilente insulin crystals, with added zinc. Combining the short-acting semilente with the slow-acting ultralente in a ratio of 3 parts semilente to 7 parts ultralente produces the intermediate-acting Lente insulin.
It is the addition of zinc and the size of their respective crystals which controls the rate of their absorption, as the only protein present in the Lente family is the insulin itself; they all have acetate buffers[18].
The phosphate buffer used for both NPH/isophane and PZI insulins is incompatible with Lente-type insulins. Phosphates alter the profile of Lente-type insulins, making them about as fast-acting as R/Neutral[19][20].
The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect[21][22], so combining them would be incompatible as well[23].
Zinc suspension | |
---|---|
Generic Names: |
|
Brand Names: |
|
Generic Names: |
|
Brand Names: |
|
Brand Names: |
|
Brand Names: |
|
Generic Names: |
ultralente |
Brand Names: |
References[]
- ↑ Diabetes Forecast-ADA, 2006-Page 5
- ↑ Endotext.com-Insulin-Pharmacology, Types of Regimens & Adjustments
- ↑ US FDA-Humulin R
- ↑ Auburn University: Insulin Preparations-Regular Insulin
- ↑ Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente Diabetes Care-1980
Note--in 1980, there was only beef Lente-type insulin--no pork or r-DNA/GE/GMLente insulins - ↑ Resource Guide-2005-American Diabetes Association
- ↑ RxEd.org-Insulin Therapy-Mixing Precautions
- ↑ Insulin-InChem
- ↑ Auburn University: Insulin Preparations-NPH
- ↑ Auburn University: Insulin Preparations
- ↑ RxEd.org-Insulin Therapy-Mixing Precautions
- ↑ Insulin-InChem
- ↑ Insulin-InChem
- ↑ Auburn University: Insulin Preparations-NPH
- ↑ Auburn University: Insulin Preparations
- ↑ RxEd.org-Insulin Therapy-Mixing Precautions
- ↑ Insulin-InChem
- ↑ Auburn University: Insulin Preparations-Lente Insulins
- ↑ Auburn University: Insulin Preparations-Lente Insulins
- ↑ RxEd.org-Insulin Therapy-Mixing Precautions
- ↑ Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente Diabetes Care-1980
Note--in 1980, there was only beef Lente-type insulin--no pork or r-DNA/GE/GMLente insulins - ↑ Resource Guide-2005-American Diabetes Association
- ↑ RxEd.org-Insulin Therapy-Mixing Precautions
- ↑ Insulin-InChem
- ↑ Insulin-InChem
- ↑ Insulin-InChem