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Absolute Bioavailability and Disposition of Lanthanum in Healthy Human Subjects Administered Lanthanum Carbonate
Author(s) -
Pennick Michael,
Dennis Kerry,
Damment Stephen J. P.
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006289846
Subject(s) - lanthanum carbonate , bioavailability , lanthanum , pharmacokinetics , chemistry , pharmacology , excretion , oral administration , hyperphosphatemia , urine , medicine , gastroenterology , kidney disease , inorganic chemistry
Lanthanum carbonate [La 2 (CO 3 ) 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 (LaCl 3 ) intravenous infusion (120 μg elemental lanthanum over a 4‐hour period), a single 1‐g oral dose [chewable La 2 (CO 3 ) 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 La 2 (CO 3 ) 3 ] was extremely low (0.00127% ± 0.00080%), with individual values in the 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.