Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia.

Abstract

The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO4 ) to healthy horses. MgSO4 is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO4 at 60mg/kg of body weight over 5min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitored and echocardiograms performed at predetermined times. Noncompartmental pharmacokinetic analysis was applied to plasma concentrations of ionized magnesium (Mg2+ ). Objective data were analyzed using the Wilcoxon rank-sum test with p<.05 used as a determination for significance. Plasma concentrations of Mg2+ increased nearly fivefold, ionized calcium (Ca2+ ) decreased by nearly 10%, and the Ca2+ to Mg2+ ratio declined more than 3.5-fold and remained different than baseline until 24hr (p<.05). Significant changes were seen with urinary fractional excretion of electrolytes, cardiovascular parameters, and echocardiographic measurements. No changes were detected in CSF electrolyte concentrations. The decrease in Ca2+ result of hypermagnesemia supports the interaction between these cations. Alterations detected in plasma electrolyte concentrations and urinary fractional excretion of electrolytes may serve as biomarkers for regulatory control for the nefarious administration of MgSO4 .