DEXTROSE 5% IN WATER FOR INTRAVENOUS INFUSION

Indication

Glucose pharmaceutical formulations (oral tablets, injections) are indicated for caloric supply and carbohydrate supplementation in case of nutrient deprivation. It is also used for metabolic disorders such as hypoglycemia.[L787]

Mechanism of Action

Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into two main phases where the preparatory phase is initiated by the phosphorylation of glucose by hexokinase to form glucose 6-phosphate.[A19402] The addition of the high-energy phosphate group activates glucose for the subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where the total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. These energy-producing reactions of glucose are limited to D-glucose as L-glucose cannot be phosphorylated by hexokinase.[T35] Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number, and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation to preserve cellular and whole body metabolic integrity.[A19401]

Pharmacokinetics

Absorption

Polysaccharides can be broken down into smaller units by pancreatic and intestinal glycosidases or intestinal flora. Sodium-dependent glucose transporter SGLT1 and GLUT2 (SLC2A2) play predominant roles in intestinal transport of glucose into the circulation.[A19395] SGLT1 is located in the apical membrane of the intestinal wall while GLUT2 is located in the basolateral membrane, but it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion.[A19400] Oral preparation of glucose reaches the peak concentration within 40 minutes and the intravenous infusions display 100% bioavailability.[A19406]

Distribution

The mean volume of distribution after intravenous infusion is 10.6L.[A19407]

Metabolism

Glucose can undergo aerobic oxidation in conjunction with the synthesis of energy molecules. Glycolysis is the initial stage of glucose metabolism where one glucose molecule is degraded into two molecules of pyruvate via substrate-level phosphorylation. These products are transported to the mitochondria where they are further oxidized into oxygen and carbon dioxide.[A19402]

Elimination

Clearance

The mean metabolic clearance rate of glucose (MCR) for the 10 subjects studied at the higher insulin level was 2.27 ± 0.37 ml/kg/min at euglycemia and fell to 1.51±0.21 ml/kg/ at hyperglycemia. The mean MCR for the six subjects studied at the lower insulin level was 1.91 ± 0.31 ml/kg/min at euglycemia.[A19408]

Toxicity

Oral LD50 value in rats is 25800mg/kg. The administration of glucose infusions can cause fluid and solute overloading resulting in dilution of the serum electrolyte concentrations, overhydration, congested states, or pulmonary edema. Hypersensitivity reactions may also occur including anaphylactic/anaphylactoid reactions from oral tablets and intravenous infusions.[L786]

Active Ingredient/Synonyms

aldehydo-D-glucose | Anhydrous dextrose | D-Glucose in linear form | D-glucose, anhydrous | D(+)-Glucose | Dextrose anhydrous | Dextrose, anhydrous | Glucose | Glucose anhydrous | Glucose, anhydrous | D-glucose |