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Lithium carbonate as a potential pharmacological vehicle: intravenous kinetics of single-dose administration in healthy subjects
Authors:Waring W Stephen  Webb David J  Maxwell Simon R J
Institution:Clinical Pharmacology Unit and Research Centre, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK. s.waring@ed.ac.uk
Abstract:OBJECTIVE: We have been developing lithium carbonate solution as a vehicle for delivery of uric acid in a research setting. We wished to determine the pharmacokinetics of a single systemic administration of 500 mg lithium carbonate (13.5 mmol free Li(+)) in healthy subjects. METHODS: Ten healthy subjects received 500 ml of a 0.1% lithium carbonate and 4% dextrose solution intravenously over 1 h. Serum lithium concentrations were determined at baseline, 15, 30, 45, 60, 75, and 90 min, and 2, 3, 7, 24, and 48 h after the start of infusion for kinetic analysis. RESULTS: Administration led to a time-dependent increase in plasma concentration, followed by a rapid decay of serum lithium concentration. Kinetic analysis showed that the pattern best fit a two-compartment model, with rapid extravascular distribution, an elimination phase half-life of 7.8+/-1.7 h, and clearance of 5.3+/-1.1 l/h. CONCLUSIONS: In healthy subjects, lithium half-life is shorter and clearance is higher than suggested by previous reports in other groups. Administration of 500 ml 0.1% lithium carbonate and 4% dextrose over 1 h is safe, well tolerated, and possibly a suitable vehicle for other agents such as uric acid.
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