Changes: Semilente

Latest revision as of 20:11, 20 August 2009

The lente types of Semilente, Lente and Ultralente are also called zinc suspension insulins.

Semilente insulin is defined as a short-acting insulin containing zinc microcrystals in an acetate buffer.^[1] This insulin is known by two other names: Prompt Zinc and Prompt Lente; this to distinguish it from the Lente and Ultralente insulins which are also part of the zinc suspension group, but whose onsets are slower and whose durations are longer. British Pharmacoepia (BP) and United States Pharmacoepia (USP)'s definitions of semilente insulin:^[2]

When reading a description of Lente insulin, the word amorphous^[3] is often used; the description is often used interchangably with the semilente term, in speaking of the 30% fraction of Lente that is semilente insulin.

While both R/neutral and semilente insulins are considered fast-acting, they differ in a few ways. There's no suspension^[4] or buffer^[5] in R/neutral; it's totally dissolved and soluble, meaning it can safely be used intravenously.

The very small insulin particles in semilente insulin are suspended by zinc^[6]. Semilente is cloudy, has an acetate buffer and cannot be used intravenously.

R/Neutral insulin cannot be reliably mixed with Lente or Ultralente insulins^[7]^[8]. Semilente can; the ratio of 3 parts semilente insulin to 7 parts ultralente insulin produces Lente insulin^[9].

Technical details

Semilente's time activity profile is very much like that of R/neutral. It begins^[10]working within 45 minutes, peaks in 2-4 hours and has a 4-6 hour duration. In dogs, both r-DNA/GE/GM and Bovine species have an onset of 10-30 minutes, peak of 1-5 hours, and duration of 4-10 hours^[11].

Unlike R/neutral, it is "cloudy", not clear, and is not soluble, therefore unable to be used intervenously.

This type of insulin was once as available as R/neutral; many people preferred it over R/neutral for bolus insulin. It has now almost disappeared entirely from the market. We know semilente best as one of the two lente-types which comprise Lente insulin; Ultralente is the other.

Semilente^[12] is unique among the fast and short-acting insulins because changes in temperature to the body do not affect its absorption rate, as is the case with the soluble insulins. A study placed people in saunas for two 25 minute periods; the intense heat had no effect on the absorption rate. This type of heat would have caused the soluble insulins to be absorbed at a faster than normal rate, bringing with it the possibility of hypoglycemia.

What Semilente Is Not

No Lente-type insulin regardless of species can contain any NPH/isophane insulin^[13] or any R/Neutral insulin^[14].

Both are chemically impossible: the phenol preservative present in NPH/isophane alters the action of Lente-type insulins, creating a mixture with an approximate action of R/Neutral.

The zinc suspension of Lente-type insulin binds R/Neutral, causing the short-acting insulin to slow, losing its short-acting effect.

Combining Lente Family Insulins

None of the Lente family of insulins (semilente, Lente, Ultralente) can be combined with^[15] NPH/isophane insulins. The phenol preservatives present in NPH-type insulins alters the Lente-types to the point where they become a close approximation of R/neutral, with regard to action^[16].

Keeping the phenol preservatives in mind, all protamine-suspended insulin mixes would be "off limits" regarding same syringe mixing with any Lente-type insulins^[17].

Insulin manufacturers^[18] indicate that R/neutral and semilente, Lente, ultralente insulins are able to be combined in the same syringe, but only just before injection. In pre-filled syringes, the zinc suspension of the Lente-type insulins binds the R/neutral, causing it to lose its short-acting effect. Various studies have documented this, and some doctors advise against using R/neutral in the same syringe with the Lente family of insulins^[19]^[20]^[21]^[22].

Specifications of semilente

Insulin Zinc Suspension BP (Amorphous)

Sterile buffered suspension of mammalian insulin in the form of a complex obtained by addition of zinc chloride. Prepared from crystalline insulin containing not less than 23 u almost colourless suspension in which the particles have no uniform shape and rarely exceed 2 m in dimension; pH 6.9 - 7.5. Iso-osmotic with blood. Containing suitable bactericide, the preparation contains 40 and 80 units/ml.

Lente insuline — Novo Nordisk Semilente MC 40- Porcine (Pork) Insulin-German Packaging. This is semilente pork insulin (Insulin vom Schwein) in U40 strength. Novo has recently discontinued this insulin^[23] and Polfa-Tarchomin (Poland) recently began producing a similar insulin.

(Note: At present, porcine semilente insulin is available only through Polfa Tarchomin, Poland. Novo Nordisk recently discontinued the product shown. It has been many years since any species of semilente has been available elsewhere, hence the lack of a UK U100 definition.)

U.S.P. describes a sterile suspension of insulin U.S.P. in buffered water for injection is modified by addition of zinc chloride so that the solid phase of suspension is amorphous. Contains 40, 80 or 100 units/ml. Also contain sodium acetate 0.15 - 0.17%, sodium chloride 0.65 - 0.75%, methyl hydroxy benzoate 0.09 - 0.11% and for each 100 units of insulin, 120 - 250 g of zinc. pH 7.2-7.5

Semilente Insulins
Short acting Non-soluble
Porcine/Pork	Novo Semilente MC

An old Novo Nordisk trade name for their semilente is Semitard.

References

[1] Insulin preparations

[2] British Pharmacoepia /United States Pharmacopeia: Definitions of Semilente Insulin

[3] Dorlands Medical Dictionary: Definition of Amorphous

[4] US FDA-Humulin R

[5] Auburn University:Insulin Preparations-Regular Insulin

[6] Auburn University: Insulin Preparations-Lente

[7] 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/GM Lente insulins

[8] Resource Guide 2005-American Diabetes Association

[9] Auburn University: insulin Preparations-Lente Insulin

[10] Wholehealthmd.com-Semilente Insulin

[11] Long-Term Management of the Diabetic Dog-2000-Drs. Fleeman & Rand (Page 2)

[12] Acta Diabetologica Latina-1983-Influence of Heat on Insulin Absorption:Different Effects on Amorphous (Semilente) & Soluble Insulins

[13] Combining Lente-type Insulins with Phenol-Preserved Insulins

[14] Lente Zinc Suspension Causes Loss Of R/Neutral Short-Acting Effect

[15] Phenol Preservatives & Lente-type Insulins--A Bad Combination

[16] RxEd.org-Insulin Therapy-Mixing Precautions

[17] RxEd.org-Insulin Therapy-Mixing Precautions

[18] Insulin Producers vs Doctors Re:Combining R/Neutral & Lente-type Insulins

[19] Availability of Soluble (R/Neutral) Insulin in Mixed Preparations of Crystalline (Lente) & Ultralente GE Insulins-Clinical Therapeutics-1991

[20] Absorption Kinetics & Action Profiles-Single Subcutaneous Administration of Human Soluble (R/Neutral) & Lente Insulin-Diabetes Care-1987

[21] Delayed Onset of Action of Soluble (R/Neutral) Insulin After Premixing With Lente Insulin Diabetes Research & Clinical Practice-1983

[22] RxEd.org-Insulin Therapy-Mixing Precautions

[23] Forum Insulin Schweiz-Novo Nordisk Withdraws Animal Insulins Worldwide

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

@@ Line 1: / Line 1: @@
 The lente types of [[Semilente]], [[Lente]] and [[Ultralente]] are also called zinc suspension insulins.
-Dorlands Medical Dictionary<ref>[http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_i_09zPzhtm#12454229 Dorlands Medical Dictionary-Semilente Insulin Definition]</ref>defines semilente insulin as a short-acting insulin containing zinc microcrystals. Merck's definition<ref>[http://www.merck.com/mrkshared/mmanual/section2/chapter13/13a.jsp Merck Manual-Definition of Semilente Insulin]</ref> is similar, adding data about the insulin having an acetate buffer.  This insulin is known by two other names: Prompt Zinc and Prompt Lente; this to distinguish it from the [[Lente]] and [[Ultralente]] insulins which are also part of the zinc suspension group, but whose [[onset]]s are slower and whose [[duration]]s are longer. British Pharmacoepia (BP) and United States Pharmacoepia (USP)'s definitions of semilente insulin:<ref>[http://www.inchem.org/documents/pims/pharm/insulin.htm British Pharmacoepia /United States Pharmacopeia: Definitions of Semilente Insulin]</ref>
+Semilente insulin is defined as a short-acting insulin containing zinc microcrystals in an acetate buffer.<ref>[http://www.auburn.edu/~deruija/insulin_preparations.pdf Insulin preparations]</ref> This insulin is known by two other names: Prompt Zinc and Prompt Lente; this to distinguish it from the [[Lente]] and [[Ultralente]] insulins which are also part of the zinc suspension group, but whose [[onset]]s are slower and whose [[duration]]s are longer. British Pharmacoepia (BP) and United States Pharmacoepia (USP)'s definitions of semilente insulin:<ref>[http://www.inchem.org/documents/pims/pharm/insulin.htm British Pharmacoepia /United States Pharmacopeia: Definitions of Semilente Insulin]</ref>
+When reading a description of [[Lente]] insulin, the word amorphous<ref> [http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSz000003784zPzhtm Dorlands Medical Dictionary: Definition of Amorphous]</ref> is often used; the description is often used interchangably with the semilente term, in speaking of the 30% fraction of Lente that is semilente insulin.
+While both [[R|R/neutral]] and semilente insulins are considered [[:Category:Fast-acting|fast-acting]], they differ in a few ways.   There's no [[suspension]]<ref>[http://www.fda.gov/cder/foi/label/2003/18780scm078,slr067_Humalog_lbl.pdf US FDA-Humulin R]</ref> or buffer<ref>[http://www.duc.auburn.edu/~deruija/insulin_preparations.pdf Auburn University:Insulin Preparations-Regular Insulin]</ref> in R/neutral; it's totally dissolved and [[soluble]], meaning it can safely be used [[:Category:Intravenous_use_YES|intravenously]].
+The very small insulin particles in semilente insulin are suspended by [[Suspension#Zinc_suspension_insulins|zinc]]<ref>[http://www.duc.auburn.edu/~deruija/insulin_preparations.pdf Auburn University: Insulin Preparations-Lente]</ref>.  Semilente is [[cloudy]], has an acetate buffer and cannot be used [[:Category:Intravenous_use_NO| intravenously]].
+R/Neutral insulin cannot be reliably mixed with [[Lente]] or [[Ultralente]] insulins<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=7192205 Intermediate-Acting Insulin Preparations: NPH (Isophane) & Lente Diabetes Care-1980]<br>Note--in 1980, there was only [[bovine|beef]] Lente-type insulin--no [[porcine|pork]] or [[r-DNA/GE/GM]][[Lente]] insulins</ref><ref>[http://www.diabetes.org/rg2005/insulin.jsp Resource Guide 2005-American Diabetes Association]</ref>.  Semilente can; the ratio of 3 parts [[semilente]] insulin to 7 parts [[ultralente]] insulin produces [[Lente]] insulin<ref>[http://www.duc.auburn.edu/~deruija/insulin_preparations.pdf Auburn University: insulin Preparations-Lente Insulin]</ref>.
-When reading a description of [[Lente]] insulin, the word amorphous<ref> [http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_a_31zPzhtm Dorlands Medical Dictionary: Definition of Amorphous]</ref> is often used; the description is often used interchangably with the semilente term, in speaking of the 30% fraction of Lente that is semilente insulin.
 ==Technical details==
-Semilente's time activity profile is very much like that of [[R]]/[[neutral]]. It begins<ref> [http://www.wholehealthmd.com/refshelf/drugs_view/1,1524,319,00.html Wholehealthmd.com-Semilente Insulin]</ref>working within 45 minutes, [[peak]]s in 2-4 hours and has a 4-6 hour [[duration]]. In dogs, both [[r-DNA/GE/GM]] and [[Bovine]] species have an onset of 10-30 minutes, peak of 1-5 hours, and duration of 4-10 hours<ref> [http://www.walthamusa.com/articles/wf103fle.pdf Long-Term Management of the Diabetic Dog-2000-Drs. Fleeman & Rand (Page 2)]</ref>.
+Semilente's time activity profile is very much like that of [[R]]/[[neutral]]. It begins<ref> [http://web.archive.org/web/20060206183330/http://www.wholehealthmd.com/refshelf/drugs_view/1,1524,319,00.html Wholehealthmd.com-Semilente Insulin]</ref>working within 45 minutes, [[peak]]s in 2-4 hours and has a 4-6 hour [[duration]]. In dogs, both [[r-DNA/GE/GM]] and [[Bovine]] species have an onset of 10-30 minutes, peak of 1-5 hours, and duration of 4-10 hours<ref> [http://www.walthamusa.com/articles/wf103fle.pdf Long-Term Management of the Diabetic Dog-2000-Drs. Fleeman & Rand (Page 2)]</ref>.
 Unlike R/neutral, it is "cloudy", not clear, and is not soluble, therefore unable to be used intervenously.
@@ Line 16: / Line 23: @@
 ==What Semilente Is Not==
-'''No''' Lente-type insulin regardless of species can contain any [[NPH]]/[[isophane]] insulin<ref>[http://www.nfb.org/vodold/vsum9809.htm Combining Lente-type Insulins with Phenol-Preserved Insulins]</ref> '''or''' any [[R]]/[[Neutral]] insulin<ref>[http://www.endotext.org/diabetes/diabetes17/diabetes17.htm Lente Zinc Suspension Causes Loss Of R/Neutral Short-Acting Effect]</ref>.
+'''No''' Lente-type insulin regardless of species can contain any [[NPH]]/[[isophane]] insulin<ref>[http://web.archive.org/web/20060427044732/http://www.nfb.org/vodold/vsum9809.htm Combining Lente-type Insulins with Phenol-Preserved Insulins]</ref> '''or''' any [[R]]/[[Neutral]] insulin<ref>[http://www.endotext.org/diabetes/diabetes17/diabetes17.htm Lente Zinc Suspension Causes Loss Of R/Neutral Short-Acting Effect]</ref>.
 Both are chemically impossible: the phenol [[preservatives|preservative]] present in [[NPH]]/[[isophane]] alters the action of Lente-type insulins, creating a  mixture with an approximate action of [[R]]/[[Neutral]].
@@ Line 30: / Line 37: @@
 |style="padding:5px;border:2px solid #ffb6c1;background-color:#ffe4e1;" width="50%"|
-None of the Lente family of insulins ([[semilente]], [[Lente]], [[Ultralente]]) can be combined with<ref>[http://www.nfb.org/vodold/vsum9809.htm Phenol Preservatives & Lente-type Insulins--A Bad Combination]</ref> [[NPH]]/[[isophane]] insulins.  The phenol [[preservatives]] present in [[NPH]]-type insulins alters the [[Lente]]-types to the point where they become a close approximation of [[R]]/[[neutral]], with regard to action.
+None of the Lente family of insulins ([[semilente]], [[Lente]], [[Ultralente]]) can be combined with<ref>[http://web.archive.org/web/20060427044732/http://www.nfb.org/vodold/vsum9809.htm Phenol Preservatives & Lente-type Insulins--A Bad Combination]</ref> [[NPH]]/[[isophane]] insulins.  The phenol [[preservatives]] present in [[NPH]]-type insulins alters the [[Lente]]-types to the point where they become a close approximation of [[R]]/[[neutral]], with regard to action<ref>[http://web.archive.org/web/20070820011317/http://www.rxed.org/rxtech/ce/tech-insulin.htm RxEd.org-Insulin Therapy-Mixing Precautions]</ref>.
-Keeping the phenol [[preservatives]] in mind, all [[protamine]]-[[Suspension|suspended]] insulin mixes would be "off limits" regarding same syringe mixing with any [[Lente]]-type insulins.
+Keeping the phenol [[preservatives]] in mind, all [[protamine]]-[[Suspension|suspended]] insulin mixes would be "off limits" regarding same syringe mixing with any [[Lente]]-type insulins<ref>[http://web.archive.org/web/20070820011317/http://www.rxed.org/rxtech/ce/tech-insulin.htm RxEd.org-Insulin Therapy-Mixing Precautions]</ref>.
 |}
-Insulin manufacturers<ref>[http://www.endotext.org/diabetes/diabetes17/diabetes17.htm Insulin Producers vs Doctors Re:Combining R/Neutral & Lente-type Insulins]</ref> indicate that [[R]]/[[neutral]] and [[semilente]], [[Lente]], [[ultralente]] insulins are able to be combined in the same syringe, but only just before injection.  In pre-filled syringes, the zinc [[suspension]] of the [[Lente]]-type insulins binds the [[R]]/[[neutral]], causing it to lose its [[short-acting]] effect. Various studies have documented this, and some doctors advise against using [[R]]/[[neutral]] in the same syringe with the [[Lente]] family of insulins<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1863938&dopt=AbstractPlus Availability of Soluble (R/Neutral) Insulin in Mixed Preparations of  Crystalline (Lente) & Ultralente GE Insulins-Clinical Therapeutics-1991]</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=3304896 Absorption Kinetics & Action Profiles-Single Subcutaneous Administration of Human Soluble (R/Neutral) & Lente Insulin-Diabetes Care-1987]</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=3545725&dopt=AbstractPlus Delayed Onset of Action of Soluble (R/Neutral) Insulin After Premixing With Lente Insulin Diabetes Research & Clinical Practice-1983]</ref>.
+Insulin manufacturers<ref>[http://www.endotext.org/diabetes/diabetes17/diabetes17.htm Insulin Producers vs Doctors Re:Combining R/Neutral & Lente-type Insulins]</ref> indicate that [[R]]/[[neutral]] and [[semilente]], [[Lente]], [[ultralente]] insulins are able to be combined in the same syringe, but only just before injection.  In pre-filled syringes, the zinc [[suspension]] of the [[Lente]]-type insulins binds the [[R]]/[[neutral]], causing it to lose its [[short-acting]] effect. Various studies have documented this, and some doctors advise against using [[R]]/[[neutral]] in the same syringe with the [[Lente]] family of insulins<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=1863938&dopt=AbstractPlus Availability of Soluble (R/Neutral) Insulin in Mixed Preparations of  Crystalline (Lente) & Ultralente GE Insulins-Clinical Therapeutics-1991]</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=3304896 Absorption Kinetics & Action Profiles-Single Subcutaneous Administration of Human Soluble (R/Neutral) & Lente Insulin-Diabetes Care-1987]</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=3545725&dopt=AbstractPlus Delayed Onset of Action of Soluble (R/Neutral) Insulin After Premixing With Lente Insulin Diabetes Research & Clinical Practice-1983]</ref><ref>[http://web.archive.org/web/20070820011317/http://www.rxed.org/rxtech/ce/tech-insulin.htm RxEd.org-Insulin Therapy-Mixing Precautions]</ref>.
 ==Specifications of semilente==
@@ Line 54: / Line 61: @@
 '''Semilente Insulins'''
 |-
-! colspan=2 align="center" style="background:powderblue;"|
+! colspan=2 align="center" style="background:lightcyan;"|
 '''[[:Category:Short-acting|Short acting]]'''<br>Non-[[soluble]]
 |-
-! width="200"align="center" style="background:lightblue;"|
+! width="200"align="center" style="background:aliceblue;"|
 [[Porcine]]/[[Pork]]
-!style="background:azure;"|[[Novo Semilente MC]]
+!style="background:ivory;"|[[Novo Semilente MC]]
 |}