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 60 mg/kg of body weight over 5 min. 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 24 hr (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.

Effects of Intravenous Magnesium Sulfate on Calcium-Regulating Hormones, Plasma and Urinary Electrolytes in Healthy Horses

“…A decrease in Ca 2+ concentrations after MgSO 4 infusion has been documented in human patients, horses and dogs [3, 19, 21-24] and could be attributed to excessive Mg 2+ activation of CaSR in the renal tubules, increasing the urinary excretion of Ca and Mg, as reported in human patients [21, 24, 25]. We anticipated this response based on a previous study where experimental hypercalcemia decreased Mg 2+ in healthy horses [4].…”

“…concentrations coupled with a high Mg 2+ /Ca 2+ ratio could be a potential biomarker for nefarious administration of MgSO 4 to competing horses [3,20].…”

“…In addition, this information may be relevant to venues such as equestrian competitions, knowing that for at least 60 minutes after administration of this dose, serum [Mg 2+ ] will be twice baseline values, potentially explaining the calming effects of hypermagnesemia and also carrying potential regulatory implications. An increase in Mg 2+ concentrations coupled with a high Mg 2+ /Ca 2+ ratio could be a potential biomarker for nefarious administration of MgSO 4 to competing horses [3, 20].…”

Effects of intravenous magnesium sulfate on serum calcium-regulating hormones and plasma and urinary electrolytes in healthy horses

“…All horses were administered a single intravenous dose of MgSO 4 (60 mg/kg) (Magnesium Sulfate 50% solution, Wedgewood Pharmacy, Swedesboro, NJ, USA) over 5 minutes to induce hypermagnesemia. This dose was chosen because it increases Mg 2+ concentrations 3-fold over baseline values, which is expected to activate CaSR, and is also the dose anecdotally used for its calming effects at equestrian events [3]. This represented approximately 30 grams of MgSO 4 (60 ml) for a 500 kg horse [3].…”

“…Intravenous magnesium sulfate (MgSO 4 ) is used in equine medicine to treat dysrhythmias, neurological disorders, hypomagnesemia in critical illness, and refractory hypocalcemia [1]. More recently, intravenous MgSO 4 has been used in equine events as a calming and performance-enhancing agent, with the ultimate goal of giving a competitive edge to horses that receive it [2,3].…”