title: Systemic lanthanum is excreted in the bile of rats.
abstract: 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 24h 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.
authors.affiliation: Shire Pharmaceuticals, Basingstoke, UK. sdamment@shire.com
authors.forename: Stephen J P
authors.initials: SJ
authors.lastname: Damment
authors.forename: Michael
authors.initials: M
authors.lastname: Pennick
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism*; D001682:Biological Availability; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005243:Feces / Q000737:chemistry; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007441:Intubation, Gastrointestinal; D007811:Lanthanum / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D012737:Sex Factors; D012965:Sodium Chloride / Q000008:administration & dosage
chemical_list: D006023:Glycoproteins; D012709:Serum Albumin; C028521:lanthanum chloride; D012965:Sodium Chloride; C119467:lanthanum carbonate; D007811:Lanthanum