The Pharmacokinetics of Potassium in Humans Is Unusual

Potassium is critical for maintaining cellular tonicity, propagation of nerve impulses, contraction of cardiac, skeletal, and smooth muscles, and normal renal function. The focus of this review is on the pharmacokinetics of potassium, K + , after administration of liquid and solid formulations of potassium chloride, KCl, to healthy subjects. Potassium can be considered an endogenous and exogenous compound. The amounts of endogenous K + are kept constant by balancing intake and loss of exogenous K + . Food and ingestion of KCl‐containing medicines are sources for exogenous K + . In the pharmacokinetic context exogenous K + from KCl‐containing medicines, K + exo,dose , is of primary interest. The distinction between the different K + entities is critical for obtaining unbiased estimates of the kinetic parameters for K + exo,dose . A literature search using prespecified acceptance criteria was performed. Publications were selected that reported plasma and urine data of K + exo,dose directly or provided information allowing their determination. Additional criteria applied included that the studies used a randomized design and controlled for the important covariates. Most of the selected publications reported urinary excretion data. Only 2 publications also reported plasma concentrations. The excursions of the plasma concentrations of K + exo,dose were considered too small to be of use by most investigators. The aggregate results indicate that urinary recovery data have the potential for providing reliable estimates for bioavailability and bioequivalence of K + exo,dose with KCl‐containing formulations. Absorption efficiency, peak rates, and corresponding times of K + exo,dose with liquid formulations are fairly consistent among studies. The mean absorption efficiency of K + exo,dose with solid and liquid formulations of KCl ranges between 70% and 90%. The absorption rate of liquid formulations is rapid, whereas the solid formulations show extended release characteristics. The time‐averaged renal clearance of K + exo,dose is about 200 mL/min during daytime and significantly smaller around midnight. Circadian rhythm and delayed homeostatic control of potassium make the pharmacokinetics of K + exo,dose time dependent. The impact of these endogenous controls makes the pharmacokinetics of K + exo,dose unusual.