Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses

Abstract

Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were administered a single intravenous dose of cobalt chloride or cobalt gluconate and serum and urine samples collected for up to 10 days post administration. Cobalt concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) and pharmacokinetic parameters determined. Additional blood samples were collected for measurement of equine EPO concentrations as well as to assess any effects on red blood cell parameters. Horses were observed for adverse effects and heart rate monitored for the first 4 h post administration. Cobalt was characterized by a large volume of distribution (0.939 L/kg) and a prolonged gamma half-life (156.4 h). Cobalt serum concentrations were still above baseline values at 10 days post administration. A single administration of cobalt had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied and no adverse effects were noted. Based on the prolonged gamma half-life and prolonged residence time, regulators should be able to detect administration of a single dose of cobalt to horses.

Pharmacokinetics of betamethasone in plasma, urine, and synovial fluid following intra‐articular administration to exercised thoroughbred horses

“…Prior to the study, horses were exercised five days a week as described previously. [9] The general exercise protocol was meant to simulate the strenuous exercise of race training. All horses were subject to regular fitness testing, including weekly heart rate measurements and calculation of V 200 (running velocity that elicited a heart rate 200 bpm) and monthly measurements of end-run plasma lactate concentrations, as a means of ensuring that the fitness level of the horses used in this study were as comparable as possible to the average Thoroughbred racehorse.…”

“…Samples were collected as described previously. [9] Catheters were removed following collection of the 18-h sample and the remaining samples collected by direct venipuncture. Blood samples were collected into ethylenediaminetetraacetic acid (EDTA) blood tubes (Kendall/Tyco Healthcare, Mansfield, MA, USA) and stored on ice until centrifugation at 3000 x g for 10 min at À4 C. Plasma was then immediately transferred into storage cryovials (Phenix Research Products, Chandler, NC, USA) and stored at À20 C until analysis (approximately 2 weeks following collection of the final sample).…”

Challenges in detecting substances for equine anti‐doping

“…Knych et al [41] , Ho et al [42] Ho et al [42] Nickel Schaumloffel et al [44] --Xenon, krypton -Thevis et al [48] -…”

“…The results showed that a single administration of cobalt had no effects on EPO concentrations, red blood cells parameters, or heart rate in any of the horses studied and no adverse effects were reported. [41] The study suggested that regulators should be able to detect administration of a single dose of cobalt to horses. Ho et al [42] conducted an extended study in which the proposed threshold concentrations of 2 ug/L in plasma and 75 ug/L in urine could be used as control limits for the detection of cobalt in horses on race-days.…”

Cobalt chloride doping in racehorses: Concerns over a potentially lethal practice

“…A recent study examined the pharmacokinetics and pharmacodynamics of cobalt following intravenous (IV) administration to 18 horses (Knych et al, 2014). The authors showed that a single IV dose of cobalt chloride or cobalt gluconate had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied.…”