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

Abstract

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.

Keywords: Bland-Altman; Wnt; compartmental; horse; laminitis; noncompartmental.