Absolute Bioavailability and Disposition of Lanthanum in Healthy Human Subjects Administered Lanthanum Carbonate


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Abstract

Lanthanum carbonate [La2(CO3)3] is a noncalcium, nonaluminum phosphate binder indicated for hyperphosphatemia treatment in end-stage renal disease. A randomized, open-label, parallel-group, phase I study was conducted to determine absolute bioavailability and investigate excretory routes for systemic lanthanum in healthy subjects. Twenty-four male subjects were randomized to a single lanthanum chloride (LaCl3 intravenous infusion (120 μg elemental lanthanum over a 4-hour period), a single 1-g oral dose [chewable La2(CO3)3 tablets; 4 × 250 mg elemental lanthanum], or no treatment (control). Serial blood, urine, and fecal samples were collected for 7 days postdosing. The absolute bioavailability of lanthanum [administered as La2(CO3)3] was extremely low (0.00127% ± 0.00080%), with individual values in them range of 0.00015% to 0.00224%. Renal clearance was negligible following oral administration (1.36±1.43 mL/min). Intravenous administration confirmed low renal clearance (0.95 ± 0.60 mL/min), just 1.7% of total plasma clearance. Fecal lanthanum excretion was not quantifiable after intravenous administration owing to high and variable background fecal lanthanum and constraints on the size of the intravenous dose. These findings demonstrate that lanthanum absorption from the intestinal tract into the systemic circulation is extremely low and that absorbed drug is cleared predominantly by nonrenal mechanisms.

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