The poor bioavailability of lanthanum carbonate means that patients receiving treatment will have low systemic exposure. However, it remains important to clearly define the metabolism, deposition and localization profile of the small fraction of absorbed lanthanum to determine any implications for long-term treatment.This presentation will deal with the fate of lanthanum in the body. Lanthanum carbonate bind strongly to phosphate in the gastrointestinal tract, forming insoluble lanthanum phosphate, excreted in faeces. Studies in humans indicate that only 0.0009% of administered lanthanum is absorbed, and, of this, less than 2% is excreted by the kidneys. Bile duct cannulation studies in rats show that the absorbed fraction is excreted by the biliary system. Plasma lanthanum levels reach a concentration of 0.5-1 ng/mL at steady state during treatment with daily oral doses of 3 g. As is the case for all cationic metals, lanthanum has the potential to deposit in bone and liver. In bone, a median concentration of 4.25 mg/g (29 nmol/g) (1.67-9.79 mg/g) is achieved after 4.5 years of oral lanthanum treatment.

X-ray fluorescence (European Synchrotron Radiation Facility, Grenoble, France) of human and rat bones after variable periods of treatment with lanthanum showed that the metal is found at both active and quiescent bone surfaces and deeper layers within the bone.  In a multicentre, randomized, open-label comparative study on the effects of lanthanum carbonate and calcium carbonate on renal bone disease, two bone biopsies (one at the start and one after 1 year of treatment) were performed in 63 dialysis patients.  We could not find any evidence of a tendency for low bone turnover (adynamic bone, osteomalacia) in dialysis patients treated orally for 1 year with lanthanum carbonate (1.25-2.5 g/day), in contrast to dialysis patients treated with calcium carbonate.  In rats, deposition of lanthanum in the liver occurred after 12 weeks of oral loading with lanthanum carbonate (2000 mg/kg/day), achieving a maximal concentration of 8.5 mg/g (59 nmol/g).  Combining transmission electron microscopy (TEM), electron energy-loss spectroscopy (EELS) and synchrotron radiation-generated X-ray fluorescence, we found lanthanum to be localized in parenchymal lysosomes but not in mitochondria or any other subcellular structure in the liver. 

The co-localization of lanthanum and iron further evidenced the element to be localized in the lysosomes.  The fact that localization of lanthanum in the liver of rats was limited to the lysosomes supports the absence of clinical hepatotoxicity in patients treated up to 6 years with lanthanum carbonate.

Lanthanum is a poorly absorbed non-metabolized element, depositing at low concentrations in the bone and liver.  No aluminium-like bone effects nor clinical hepatotoxicity has been observed after chronic treatment with lanthanum carbonate.