Pharmacokinetics of intravenous lithium chloride and assessment of agreement between two methods of lithium concentration measurement in the horse

• Published in: Equine veterinary journal 2018-07, Vol.50 (4), p.537-543
• Main Authors: Martin, L. M., Bukoski, A. D., Whelchel, D. D., Evans, T. J., Wiedmeyer, C. E., Black, S. J., Johnson, P. J.
• Format: Article
• Language: English
• Subjects: Agreements; Bland–Altman; Coefficient of variation; compartmental; horse; Horses; Intravenous administration; laminitis; Linearity; Lithium; Lithium chloride; Mass spectrometry; Mass spectroscopy; Measurement methods; noncompartmental; Pharmacokinetics; Side effects; Spectrophotometry; Toxicity; Wnt
• ISSN: 0425-1644; 2042-3306
• DOI: 10.1111/evj.12778

Summary Background Pharmacokinetics of lithium chloride (LiCl) administered as a bolus, once i.v. have not been determined in horses. There is no point‐of‐care test to measure lithium (Li+) concentrations in horses in order to monitor therapeutic levels and avoid toxicity. Objectives To determine the pharmacokinetics of LiCl in healthy adult horses and to compare agreement between two methods of plasma Li+ concentration measurement: spectrophotometric enzymatic assay (SEA) and inductively coupled plasma mass spectrometry (ICP‐MS). Study design Nonrandomised, single exposure with repeated measures over time. Methods Lithium chloride was administered (0.15 mmol/kg bwt) as an i.v. bolus to eight healthy adult horses. Blood samples were collected pre‐administration and at multiple times until 48 h post‐administration. Samples were analysed by two methods (SEA and ICP‐MS) to determine plasma Li+ concentrations. Pharmacokinetics were determined based on the reference ICP‐MS data. Results Adverse side effects were not observed. The SEA showed linearity, R2 = 0.9752; intraday coefficient of variation, 2.5%; and recovery, 96.3%. Both noncompartmental and compartmental analyses (traditional two‐stage and nonlinear mixed‐effects [NLME] modelling) were performed. Geometric mean values of noncompartmental parameters were plasma Li+ concentration at time zero, 2.19 mmol/L; terminal elimination half‐life, 25.68 h; area under the plasma concentration–time curve from time zero to the limit of quantification, 550 mmol/L min; clearance, 0.273 mL/min/kg; mean residence time, 31.22 h; and volume of distribution at steady state, 511 mL/kg. Results of the traditional two‐stage analysis showed good agreement with the NLME modelling approach. Bland–Altman analyses demonstrated poor agreement between the SEA and ICP‐MS methods (95% limits of agreement = 0.14 ± 0.13 mmol/L). Main limitations Clinical effects of LiCl have not been investigated. Conclusions The LiCl i.v. bolus displayed pharmacokinetics similar to those reported in other species. The SEA displayed acceptable precision but did not agree well with the reference method (ICP‐MS). The Summary is available in Spanish – see Supporting Information