Actions of Glarine in details
Pharmacology: Pharmacodynamics: The primary activity of insulin, including Glarine, is regulation of glucose metabolism. Insulin and its analogues lower blood glucose levels bu stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis.
Glarine differs from other insulins because its unique structure provides a smooth and peakless profile with a prolonged duration of action of 24 hrs (end of observation period) compared to 14.5 hrs for neutral protamine hagedorn (NPH) human insulin.
In clinical studies, IV Glarine and human insulin have been shown to be equipotent when given at the same doses. The onset of action of Glarine is slower than NPH human insulin. The effect profile of Glarine is smooth and peakless, and the duration of its effect is prolonged compared to NPH human insulin.
Pharmacokinetics: After SC injection of Glarine, the insulin serum concentrations indicate a slower, more prolonged absorption and a lack of a peak in comparison to NPH human insulin. Concentrations are, thus, consistent with the time profile of the pharmacodynamic activity of Glarine.
Glarine is a human insulin analogue that has been designed to have low solubility at neutral pH. At pH 4, the pH of the Glarine injection solution, it is completely soluble. After injection into the SC tissue, the acidic solution is neutralized, leading to formation of microprecipitates from which small amounts of Glarine are continuously released, providing a smooth, peakless, predictable time/concentration profile and a prolonged duration of action. This allows once daily dosing to meet a patient's basal insulin needs.
Glarine is partly degraded in the SC depot at the carboxyl terminus of the B-chain to form the active metabolites, with similar in vitro activity to insulin.
How should I take Glarine?
A nurse or other trained health professional may give you Glarine, recombinant. You may also be taught how to give your medicine at home. Glarine, recombinant is given as a shot under your skin.
Each package of Glarine contains a patient information sheet. Read this sheet carefully and make sure you understand:
- How to prepare the medicine.
- How to inject the medicine.
- How to dispose of syringes, needles, and injection devices.
It is best to use a different place on the body for each injection (eg, under the skin of your abdomen or stomach, thigh, or upper arm). If you have questions about this, contact a member of your health care team.
Since Glarine lowers the blood glucose over 24 hours, it should be taken once daily at bedtime.
The insulin solution should look clear and colorless. Do not use Glarine if it is cloudy or thickened.
Follow carefully the special meal plan your doctor gave you. This is the most important part of controlling your condition, and is necessary if the medicine is to work properly. Also, exercise regularly and test for sugar in your blood or urine as directed.
Dosing
The dose of Glarine, recombinant will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Glarine, recombinant. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For injection dosage form:
- Lantus®:
- For type 2 diabetes mellitus:
- Adults and children 6 years of age and older—Dose is based on your blood sugar and must be determined by your doctor.
- Children younger than 6 years of age—Use and dose must be determined by your doctor.
- For type 2 diabetes mellitus:
- Glarine®:
- For type 1 or type 2 diabetes mellitus:
- Adults—Dose is based on your blood sugar and must be determined by your doctor.
- Children—Use and dose must be determined by your doctor.
- For type 1 or type 2 diabetes mellitus:
- Lantus®:
Storage
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
Store unused cartridge or SoloStar® prefilled pens in the refrigerator. Protect from light. Do not freeze.
The SoloStar® prefilled pen that you are currently using should not be refrigerated. You should store the pen at room temperature, away from direct heat and light. Throw away any opened prefilled pen after 28 days.
After a cartridge has been inserted into a pen, store the cartridge and pen at room temperature, not in the refrigerator.
Glarine administration
SubQ: Do not use if solution is viscous or cloudy; use only if clear and colorless with no visible particles. Glarine should be administered consistently at the same time each day. Cold injections should be avoided. SubQ administration is usually made into the thighs, arms, buttocks, or abdomen; absorption rates vary amongst injection sites; be consistent with area used while rotating injection sites within the same region to avoid lipodystrophy or localized cutaneous amyloidosis. Rotating from an injection site where lipodystrophy/cutaneous amyloidosis is present to an unaffected site may increase risk of hypoglycemia. Do not dilute or mix Glarine with any other insulin formulation or solution. Glarine prefilled pens are available in concentrations of 100 units/mL and 300 units/mL. Prefilled pens are calibrated to display the actual insulin units administered (no dosage conversion needed) and will administer up to 80 units per injection, in 1 unit increments (Lantus SoloStar, Basaglar KwikPen, Basaglar Tempo Pen, Glarine SoloStar) or up to 160 units per injection, in 2 unit increments (Glarine Max SoloStar, Glarine DoubleStar [Canadian product]). Glarine Max SoloStar and Glarine DoubleStar (Canadian product) prefilled pens are only recommended for use in patients requiring at least 20 units of Glarine per day. Do not use a syringe to withdraw concentrated Glarine (300 units/mL) from a prefilled pen for administration. Cartridges (Canadian product) are to be used only with reusable pens recommended by the manufacturer (refer to product labeling).
Glarine pharmacology
Mechanism of Action
The primary activity of insulin, including Glarine, is regulation of glucose metabolism. Insulin and its analogs lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.
Pharmacodynamics
Onset of Action
The pharmacodynamic profiles for Glarine given subcutaneously as a single dose of 0.4, 0.6, or 0.9 U/kg in a euglycemic clamp study in patients with type 1 diabetes showed that on average, the onset of action develops over 6 hours post-dose for all three single doses of Glarine.
Single Dose Pharmacodynamics
The pharmacodynamics for single 0.4, 0.6, and 0.9 U/kg doses of Glarine in 24 patients with type 1 diabetes mellitus was evaluated in a euglycemic clamp study. On a unit-to-unit basis, Glarine had a lower maximum (GIRmax) and 24 hour glucose lowering effect (GIR-AUC0–24) compared to LANTUS. The overall glucose lowering effect of Glarine 0.4 U/kg was 12% of the glucose lowering effect of an equivalent dose of LANTUS. Glucose lowering at least 30% of the effect of a single 0.4 U/kg dose of LANTUS was not observed until the single dose of Glarine exceeded 0.6 U/kg.
Multiple Once Daily Dose Pharmacodynamics
The pharmacodynamics of Glarine after 8 days of daily injection was evaluated in 30 patients with type 1 diabetes. At steady state, the 24 hour glucose lowering effect (GIR-AUC0–24) of Glarine 0.4 U/kg was approximately 27% lower with a different distribution profile than that of an equivalent dose of LANTUS. The glucose lowering effect of a Glarine dose increased with each daily administration.
The pharmacodynamic profile for Glarine given subcutaneously as multiple once-daily subcutaneous injections of 0.4 U/kg in a euglycemic clamp study in patients with type 1 diabetes, is shown in Figure 1.
Figure 1: Glucose infusion rate in Patients with type 1 diabetes in multiple dose administration of Glarine
Glucose infusion rate: determined as amount of glucose infused to maintain constant plasma glucose levels.
Pharmacokinetics
Absorption and Bioavailability
The pharmacokinetic profiles for single 0.4, 0.6, and 0.9 U/kg doses of Glarine in 24 patients with type 1 diabetes mellitus was evaluated in a euglycemic clamp study. The median time to maximum serum insulin concentration was 12 (8–14), 12 (12–18), and 16 (12–20) hours, respectively. Mean serum insulin concentrations declined to the lower limit of quantitation of 5.02 µU/mL by 16, 28, and beyond 36 hours, respectively.
Steady state insulin concentrations are reached by at least 5 days of once daily subcutaneous administration of 0.4 U/kg to 0.6 U/kg doses of Glarine over 8 days in patients with type 1 diabetes mellitus.
After subcutaneous injection of Glarine, the intra-subject variability, defined as the coefficient of variation for the insulin exposure during 24 hours was 21.0% at steady state.
Elimination
After subcutaneous injection of Glarine in diabetic patients, Glarine is metabolized at the carboxyl terminus of the B-chain with formation of two active metabolites M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin). The in vitro activity of M1 and M2 were similar to that of human insulin.
Specific Populations
Age (Geriatric Population and Pediatric Population), Race, and Sex: Effect of age, race, and sex on the pharmacokinetics of Glarine has not been evaluated.
Obesity: Effect of BMI on the pharmacokinetics of Glarine has not been evaluated.
Reviews
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Information checked by Dr. Sachin Kumar, MD Pharmacology
