Lanthanum carbonate: a review of its use in lowering serum phosphate in patients with end-stage renal disease.

Orally administered lanthanum carbonate (Fosrenol®) dissociates in the acid environment of the upper gastrointestinal tract to release the cation lanthanum, which then binds dietary phosphate. Lanthanum carbonate was effective in reducing levels of serum phosphate and serum calcium x phosphate product and then maintaining these levels within target ranges for up to 6 years in adult patients with end-stage renal disease (ESRD) on haemodialysis or peritoneal dialysis. The reduction in serum phosphate levels with lanthanum carbonate was generally similar to that with calcium carbonate or sevelamer hydrochloride. This agent was generally well tolerated, with the most frequently reported adverse events being gastrointestinal in nature and occurring at a similar rate to that with calcium carbonate. However, lanthanum carbonate was associated with fewer episodes of hypercalcaemia than calcium carbonate. Overall, lanthanum carbonate is a valuable option for the reduction of serum phosphate levels in patients with ESRD on haemodialysis or peritoneal dialysis. Pharmacological Lanthanum carbonate dissociates in the acid environment of the upper gastro-Properties intestinal tract to release the trivalent cation lanthanum, which binds with high affinity to dietary phosphate in the stomach and upper small intestine, forming insoluble lanthanum phosphate. Lanthanum carbonate reduces daily phosphate absorption. In patients with chronic kidney disease with residual kidney function, the decrease in urinary phosphate excretion (=300 mg/day) achieved with lanthanum carbonate ≤3000 mg/day was estimated to be equivalent to about one-third of the daily phosphate absorption. Lanthanum carbonate was not associated with detrimental effects on bone-cell activity, according to paired-bone biopsy studies of up to 2 years duration in patients with ESRD. With lanthanum carbonate versus comparator phosphate binder therapy, the percentage of patients with improved bone turnover after 1 year, but not 2 years, was significantly higher, and the percentage of patients with reduced bone volume was significantly lower after 2 years. Lanthanum does not appear to cross the blood-brain barrier, according to data from animal studies. In patients with ESRD undergoing haemodialysis, there was no significant difference between lanthanum carbonate and alternative phosphate binder therapy in the decline in cognitive function that occurred over a 2-year period. Systemic absorption of lanthanum carbonate is minimal (absolute bioavailability <0.002%). In patients with ESRD administered lanthanum carbonate 3000 mg/day for 10 days, the mean maximum plasma concentration of lanthanum was 1.0 ng/mL. Plasma concentrations of lanthanum did not increase with long-term (up to 6 years) administration of lanthanum carbonate. Bone biopsies taken from patients with ESRD who were treated with lanthanum carbonate for up to 4.5 years indicated an increase in bone lanthanum concentrations over the treatment phase (maximum concentration in any individual patient ≈10 μg/g wet weight bone). After treatment cessation, lanthanum loss from bone was estimated to be =13% per year. In long-term animal studies, lanthanum concentrations increased over time in several tissues, including the liver; however, there was no evidence of adverse effects of this agent on the liver in clinical studies in which patients with ESRD received up to 6 years of lanthanum carbonate treatment.