Potassium chloride

Active ion transport by the sodium-potassium ATP ASE carrier maintains a high gradient of potassium across the plasma membrane. Intracellular concentrations of potassium are about 150 mEq per litre while the plasma concentration is in the range of 3.5 to 5 mEq per litre, although there is a modest variation from one cell type to another.

Potassium plays a vital physiological role in maintenance of normal electrical excitability of nerve and muscle. It is also important in the genesis and correction of imbalances of acid-base metabolism.

In acute hypokalaemia, parenteral administration of potassium chloride promptly corrects the deficit in plasma potassium concentration and restores normal physiological function to potassium-dependent systems.

Oral administration

The potassium chloride in extended-release tablet is completely absorbed before it leaves the small intestine. The wax matrix is not absorbed and is excreted in the feces; in some instances the empty matrices may be noticeable in the stool. When the bioavailability of the potassium ion from the extended-release tablet is compared to that of a true solution the extent of absorption is similar.

The extended-release properties of extended-release tablet are demonstrated by the finding that a significant increase in time is required for renal excretion of the first 50% of the extended-release dose as compared to the solution.

Increased urinary potassium excretion is first observed 1 hour after administration of extended-release tablet, reaches a peak at approximately 4 hours, and extends up to 8 hours.

Mean daily steady-state plasma levels of potassium following daily administration of extended-release tablets cannot be distinguished from those following administration of potassium chloride solution or from control plasma levels of potassium ion.

Based on published literature, the rate of absorption and urinary excretion of potassium from KCl oral solution were higher during the first few hours after dosing relative to modified release KCl products. The bioavailability of potassium, as measured by the cumulative urinary excretion of K⁺ over a 24 hour post dose period, is similar for KCl solution and modified release products.

Specific Populations

Cirrhotics

Based on published literature, the baseline corrected serum concentrations of potassium measured over 3 hours after administration in cirrhotic subjects who received an oral potassium load rose to approximately twice that of normal subjects who received the same load.

IV administration

Potassium is an essential dietary constituent and is readily absorbed from the gastro-intestinal tract. Accumulation of potassium by cells occurs via an energy-dependent mechanism that extrudes sodium. Active ion transport systems maintain a high gradient of potassium across the plasma membrane, resulting in plasma concentrations of about 3.5 to 5 mEq per litre and intracellular concentrations of approximately 150 mEq per litre.

Potassium is excreted mainly by the kidneys. It is freely filtered at the glomerulus and is mainly absorbed in the proximal tubules, so that by the time the tubuler fluid reaches the late distal tubules, it contains less than 10% of the amount of potassium in the original glomerular filtrate. Normally, considerable amounts of potassium are secreted into the distal tubules and secretory transport is extremely important for the control of plasma potassium concentration.

As a consequence of the large volume of distribution and the rapid response of the kidney, intracellular and extracellular concentrations of potassium are normally maintained within relatively narrow limits. However, when potassium is administered as a drug, the factors that govern the rate and extent of its distribution are of critical importance. Although administration of potassium will not significantly increase the total body content of the ion, it may easily raise the extracellular concentration excessively. Because it is the extracellular concentration of potassium that determines life-threatening toxicity, awareness of the transient concentration achieved in plasma should govern the use of potassium therapy.