Systemic lanthanum is excreted in the bile of rats

Lanthanum carbonate is a non-calcium-based oral phosphate binder for the control of hyperphosphataemia in patients with chronic kidney disease Stage 5. As part of its pre-clinical safety evaluation, studies were conducted in rats to determine the extent of absorption and routes of excretion. Following oral gavage of a single 1500 mg/kg dose, the peak plasma lanthanum concentration was 1.04 +/- 0.31 ng/mL, 8 h post-dose. Lanthanum, was almost completely bound to plasma proteins (> 99.7%). Within 24 h of administration of a single oral dose, 97.8 +/- 2.84% of the lanthanum was recovered in the faeces of rats. Comparing plasma exposure after oral and intravenous administration of lanthanum yielded an absolute oral bioavailability of 0.0007%. Following intravenous administration of lanthanum chloride (0.3 mg/kg), 74.1 5.82% of the dose (96.9 0.50% of recovered lanthanum) was excreted in faeces in 42 days, and in bile-duct cannulated rats, 10.0 2.46% of the dose (85.6 2.97% of recovered lanthanum) was excreted in bile in 5 days. Renal excretion was negligible, with < 2% of the intravenous dose recovered in urine. These studies demonstrate that lanthanum undergoes extremely low intestinal absorption and that absorbed drug is predominantly excreted in the bile. (c) 2007 Elsevier Ireland Ltd. All rights reserved.