Mag-Tab SR Mechanism of Action

Pharmacology: Magnesium is the fourth most abundant cation in the body and the second (after potassium) most abundant intracellular cation. Magnesium plays a critical role in a variety of cell functions and regulates many receptor systems that use adenosine triphosphate (ATP). It has been identified as a cofactor in over 300 enzymatic reactions involving energy metabolism and protein and nucleic acid synthesis.
Mg++ is an essential factor in regulating ion transport in and out of cells, and stabilizes cell membrane permeability and electrolyte balance. Mg++ ions are a cofactor for the normal functioning of the ATP-dependent sodium-potassium "pump" found in muscle membrane. The efficiency of the pump is compromised without magnesium. A high frequency of hypomagnesemia occurs in concert with other electrolyte abnormalities (see Figure 1 as follows). Many clinicians believe that hypomagnesemia is an important component of hypokalemia. Calcium is a direct antagonist of magnesium and hypercalcemia can lead to cases of hypomagnesemia. Magnesium opposes the entry of Ca++ into cells and blood vessel walls and serves as a "natural calcium channel blocker". (See Figure 1.)

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Systemically, magnesium lowers blood pressure and alters peripheral resistance in patients with low serum Mg++ levels. Mg++ homeostasis disturbances are fairly common in clinical practice, e.g., hypomagnesemia associated with patients receiving diuretic therapy, and diabetic patients whose disease causes glycosuria leading to significant renal magnesium wasting.
Pharmacokinetics: Magnesium balance is a function of intake and excretion. Magnesium absorption occurs primarily in the distal small intestine, (jejunum and ileum), although a small amount is absorbed in the colon. Solubility and absorption of Mg++ across a range of pH's are necessary to correct deficiencies.
Normal individuals need to ingest 0.3 to 0.4 mEq/kg/d to stay in balance. Of the total amount ingested, approximately 30% to 40% is absorbed, primarily in the small bowel, through both a transport system and passive diffusion resulting from the bulk flow of water. Unlike calcium, there is no active transport system for Mg++ re-absorption in the small intestine. Two other processes take place in the gut: [i] Mg++ secretion of approximately 40 mg (1.7 mmol) in the intestinal secretions; and [ii] absorption of 20 mg (0.8 mmol) in the sigmoid colon.
The kidney is the major regulator of serum magnesium levels. In the healthy adult, there is no net gain or loss of Mg++ from bone and the overall Mg balance is achieved by the urinary excretion of approximately 100 mg (4.1 mmol) or about one-third of what is absorbed.
Figure 2 as follows shows the distribution of Mg in the body. (See Figure 2.)

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While only 1% of body Mg++ is distributed extracellularly (which does not reflect intracellular levels), serum Mg++ levels should still be tested to detect cases of obvious magnesium deficiency. The normal range for serum Mg++ in adults is 1.6 to 2.5 mEq/dL.
Figure 3 as follows shows how Mag-Tab SR can improve low levels of serum Mg++ absolutely and comparatively.
Mag-Tab SR is the gray line and enteric coated magnesium chloride is the black line. (See Figure 3.)

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Absorption: Unlike other oral Mg++ supplements with low or marginal solubility, the Mag-Tab SR (magnesium L-lactate dihydrate) formulation provides more soluble, absorbable and bioavailable Mg++ across a range of pH's. (See Table 1.)
Figure 4 shows that serum Mg levels were significantly higher (p<0.05) in normal subjects after administration of Mag-Tab SR vs. Enteric coated magnesium chloride. (See Figure 4.)

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Distribution: Magnesium is distributed throughout the body with approximately one-half of the total Mg++ in soft tissue, the majority of the remaining Mg++ is in bone and less than 1% in the blood. Normal serum Mg concentrations range from 1.6 to 2.5 mEq/dL in adults, 1.6 to 2 mEq/dL in children and 1.6 to 2.3 mEq/dL in neonates and infants.
Magnesium crosses the placenta and is excreted into breast milk; however, problems in humans have not been reported. Magnesium passes into spinal fluid at levels of 2.0 to 2.5 mEq/dL.
Metabolism/Excretion: Magnesium is not metabolized. The kidneys regulate elimination and the rate of excretion varies with the patient's condition and level of hypo-, hyper-, or normomagnesemia. Eighty percent of plasma Mg++ is unbound and available for glomerular filtration. Under normal conditions, 95% of the filtered load is reabsorbed by the kidney and 5% (about 100 mg of total) appears in the urine. In clinical conditions of Mg++ deficiency, the kidney can decrease the amount excreted to less than 0.5% of the filtered load. Conversely, in conditions of hypermagnesemia or magnesium infusion, the kidney has the ability to increase the excretion of Mg++ to 40% to 80% of the filtered load.
Solubility of Magnesium Lactate and Magnesium Oxide: See Figure 5.

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Comparative Solubility of Mag-Tab SR and Magnesium Oxide in Simulated Gastric and Intestinal Fluid at various pH's: A comparative solubility experiment reveals that regardless of the pH magnesium lactate is soluble and available for absorption. (See Table 1.)

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Serum and Urine Absorption Studies of Mag-Tab SR: See Tables 2, 3 and 4.

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Comparative Study: Mag-Tab SR vs. Slow Mag: Magnesium L-lactate dihydrate bioavailability not impaired by decreased gastric activity. (See Table 5.)

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Solubility, Absorption and Bioavailability: See Table 6.

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