The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Geert J. Behets - One of the best experts on this subject based on the ideXlab platform.
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Use of Lanthanum for water treatment A matter of concern
Chemosphere, 2019Co-Authors: Geert J. Behets, Kayawe Valentine Mubiana, Ludwig V. Lamberts, Karin Finsterle, Nigel Traill, Ronny Blust, Patrick C. D'haeseAbstract:Abstract Among several other eutrophication management tools, Phoslock®, a Lanthanum modified bentonite (LMB) clay, is now frequently used. Concerns have been raised as to whether exposure to Phoslock®-treated water may lead to Lanthanum accumulation/toxicity in both animals and humans. In the present experimental study, rats were administered Lanthanum orally as either Lanthanum carbonate, Lanthanum chloride or Phoslock® at doses of either 0.5 or 17 mg/L during 10 weeks. Controls received vehicle. The gastrointestinal absorption and tissue distribution of Lanthanum was investigated. Extremely strict measures were implemented to avoid cross-contamination between different tissues or animals. Results showed no differences in gastrointestinal absorption between the different compounds under study as reflected by the serum Lanthanum levels and concentrations found in the brain, bone, heart, spleen, lung, kidney and testes. At sacrifice, significant but equally increased Lanthanum concentrations versus vehicle were observed in the liver for the highest dose of each compound which however, remained several orders of magnitude below the liver Lanthanum concentration previously measured after long-term therapeutic administration of Lanthanum carbonate and for which no hepatotoxicity was noticed in humans. In conclusion, (i) the use of LMB does not pose a toxicity risk (ii) gastrointestinal absorption of Lanthanum is minimal and independent on the type of the compound, (iii) with exception of the liver, no significant increase in Lanthanum levels is observed in the various organs under study, (iv) based on previous studies, the slightly increased liver Lanthanum levels observed in a worst case scenario do not hold any risk of hepatotoxicity.
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hepatocellular transport and gastrointestinal absorption of Lanthanum in chronic renal failure
Kidney International, 2009Co-Authors: An R. Bervoets, Stephen J.p. Damment, Geert J. Behets, Steven C. Verberckmoes, D Schryvers, Frank Roels, Zhang Yang, Simonne Dauwe, Valentine K Mubiana, Ronny BlustAbstract:Lanthanum carbonate is a new phosphate binder that is poorly absorbed from the gastrointestinal tract and eliminated largely by the liver. After oral treatment, we and others had noticed 2–3 fold higher Lanthanum levels in the livers of rats with chronic renal failure compared to rats with normal renal function. Here we studied the kinetics and tissue distribution, absorption, and subcellular localization of Lanthanum in the liver using transmission electron microscopy, electron energy loss spectrometry, and X-ray fluoresence. We found that in the liver Lanthanum was located in lysosomes and in the biliary canal but not in any other cellular organelles. This suggests that Lanthanum is transported and eliminated by the liver via a transcellular, endosomal-lysosomal-biliary canicular transport route. Feeding rats with chronic renal failure orally with Lanthanum resulted in a doubling of the liver levels compared to rats with normal renal function, but the serum levels were similar in both animal groups. These levels plateaued after 6 weeks at a concentration below 3 μg/g in both groups. When Lanthanum was administered intravenously, thereby bypassing the gastrointestinal tract-portal vein pathway, no difference in liver levels was found between rats with and without renal failure. This suggests that there is an increased gastrointestinal permeability or absorption of oral Lanthanum in uremia. Lanthanum levels in the brain and heart fluctuated near its detection limit with long-term treatment (20 weeks) having no effect on organ weight, liver enzyme activities, or liver histology. We suggest that the kinetics of Lanthanum in the liver are consistent with a transcellular transport pathway, with higher levels in the liver of uremic rats due to higher intestinal absorption.
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Lanthanum a safe phosphate binder
Seminars in Dialysis, 2006Co-Authors: Veerle P. Persy, Marc E. De Broe, Geert J. Behets, An R. Bervoets, Patrick C DhaeseAbstract:: Accumulation of inorganic phosphate due to renal functional impairment contributes to the increased cardiovascular mortality observed in dialysis patients. Phosphate plays a causative role in the development of vascular calcification in renal failure; treatment with calcium-based phosphate binders and vitamin D can further increase the Ca x PO(4) product and add to the risk of ectopic mineralization. The new generation of calcium-free phosphate binders, sevelamer and Lanthanum, can control hyperphosphatemia without adding to the patients calcium load. In this article, the metabolism of Lanthanum carbonate and its effects in bone, liver and brain are discussed. Although Lanthanum is a metal cation its effects are not comparable to those of aluminum. Indeed, in clinical studies no toxic effects of Lanthanum have been reported after up to four years of follow-up. The bioavailability of Lanthanum is extremely low. The effects observed in bone are due to phosphate depletion, with no signs of direct bone toxicity yet observed in rats or humans. The liver is the main route of excretion for Lanthanum carbonate, which can be localized in the lysosomes of hepatocytes. No Lanthanum could be detected in brain tissue.
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Localization of Lanthanum in bone of chronic renal failure rats after oral dosing with Lanthanum carbonate
Kidney International, 2005Co-Authors: Geert J. Behets, Marc E. De Broe, Steven C. Verberckmoes, Line Oste, An R. Bervoets, Murielle Salomé, Alan G. Cox, John Denton, Patrick C. D'haeseAbstract:Localization of Lanthanum in bone of chronic renal failure rats after oral dosing with Lanthanum carbonate. Background Lanthanum carbonate has been shown to be a safe, effective phosphate-binding agent. We have shown that an impaired mineralization in chronic renal failure rats treated with high doses of Lanthanum carbonate develops secondary to phosphate depletion and is therefore pharmacologically mediated rather than a direct effect of Lanthanum on bone. Although bulk bone Lanthanum concentrations are low, it is important to consider the localization within a given tissue. Methods Using the scanning x-ray micro-fluorescence set-up at beamline ID21 of the European Synchrotron Radiation Facility, calcium and Lanthanum distributions in bone samples were mapped. Results In chronic renal failure rats loaded orally with Lanthanum carbonate (12 weeks) (2000 mg/kg/day), bulk bone Lanthanum concentrations reached values up to 5 μg/g wet weight. Lanthanum could be demonstrated at the edge of the mineralized bone, at both actively mineralizing and quiescent sites, independent of the type of bone turnover. In the presence of hyperparathyroid bone disease, Lanthanum was also distributed throughout the mineralized trabecular bone. No correlation with the presence of osteoid, or the underlying bone pathology could be demonstrated. After a 2- or 4-week washout period before sacrifice, Lanthanum localization did not change significantly. Conclusion The comparable localization of Lanthanum in different types of bone turnover, and the unchanged localization after washout and consequent disappearance of the mineralization defect, indicates no relationship between the localization of Lanthanum in bone and the presence of a mineralization defect.
Patrick C. D'haese - One of the best experts on this subject based on the ideXlab platform.
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Use of Lanthanum for water treatment A matter of concern
Chemosphere, 2019Co-Authors: Geert J. Behets, Kayawe Valentine Mubiana, Ludwig V. Lamberts, Karin Finsterle, Nigel Traill, Ronny Blust, Patrick C. D'haeseAbstract:Abstract Among several other eutrophication management tools, Phoslock®, a Lanthanum modified bentonite (LMB) clay, is now frequently used. Concerns have been raised as to whether exposure to Phoslock®-treated water may lead to Lanthanum accumulation/toxicity in both animals and humans. In the present experimental study, rats were administered Lanthanum orally as either Lanthanum carbonate, Lanthanum chloride or Phoslock® at doses of either 0.5 or 17 mg/L during 10 weeks. Controls received vehicle. The gastrointestinal absorption and tissue distribution of Lanthanum was investigated. Extremely strict measures were implemented to avoid cross-contamination between different tissues or animals. Results showed no differences in gastrointestinal absorption between the different compounds under study as reflected by the serum Lanthanum levels and concentrations found in the brain, bone, heart, spleen, lung, kidney and testes. At sacrifice, significant but equally increased Lanthanum concentrations versus vehicle were observed in the liver for the highest dose of each compound which however, remained several orders of magnitude below the liver Lanthanum concentration previously measured after long-term therapeutic administration of Lanthanum carbonate and for which no hepatotoxicity was noticed in humans. In conclusion, (i) the use of LMB does not pose a toxicity risk (ii) gastrointestinal absorption of Lanthanum is minimal and independent on the type of the compound, (iii) with exception of the liver, no significant increase in Lanthanum levels is observed in the various organs under study, (iv) based on previous studies, the slightly increased liver Lanthanum levels observed in a worst case scenario do not hold any risk of hepatotoxicity.
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Localization of Lanthanum in bone of chronic renal failure rats after oral dosing with Lanthanum carbonate
Kidney International, 2005Co-Authors: Geert J. Behets, Marc E. De Broe, Steven C. Verberckmoes, Line Oste, An R. Bervoets, Murielle Salomé, Alan G. Cox, John Denton, Patrick C. D'haeseAbstract:Localization of Lanthanum in bone of chronic renal failure rats after oral dosing with Lanthanum carbonate. Background Lanthanum carbonate has been shown to be a safe, effective phosphate-binding agent. We have shown that an impaired mineralization in chronic renal failure rats treated with high doses of Lanthanum carbonate develops secondary to phosphate depletion and is therefore pharmacologically mediated rather than a direct effect of Lanthanum on bone. Although bulk bone Lanthanum concentrations are low, it is important to consider the localization within a given tissue. Methods Using the scanning x-ray micro-fluorescence set-up at beamline ID21 of the European Synchrotron Radiation Facility, calcium and Lanthanum distributions in bone samples were mapped. Results In chronic renal failure rats loaded orally with Lanthanum carbonate (12 weeks) (2000 mg/kg/day), bulk bone Lanthanum concentrations reached values up to 5 μg/g wet weight. Lanthanum could be demonstrated at the edge of the mineralized bone, at both actively mineralizing and quiescent sites, independent of the type of bone turnover. In the presence of hyperparathyroid bone disease, Lanthanum was also distributed throughout the mineralized trabecular bone. No correlation with the presence of osteoid, or the underlying bone pathology could be demonstrated. After a 2- or 4-week washout period before sacrifice, Lanthanum localization did not change significantly. Conclusion The comparable localization of Lanthanum in different types of bone turnover, and the unchanged localization after washout and consequent disappearance of the mineralization defect, indicates no relationship between the localization of Lanthanum in bone and the presence of a mineralization defect.
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Improving outcomes in hyperphosphataemia.
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2004Co-Authors: Marc E. De Broe, Patrick C. D'haeseAbstract:Preclinical studies have shown that Lanthanum has a very high phosphate-binding capacity at gastrointestinal pH, while clinical trials have shown Lanthanum carbonate to be an effective, well-tolerated phosphate binder for the treatment of hyperphosphataemia in patients with end-stage renal disease. Optimization of bone health is an important issue in these patients, and, based on theoretical grounds, there have been concerns that Lanthanum will have toxic effects on bone similar to those of aluminium. However, compared with aluminium, absorption of Lanthanum is extremely low and Lanthanum treatment is not associated with systemic toxicity. In addition, unlike aluminium, elimination of Lanthanum is not through the kidney, but mainly takes place via the biliary route and is, therefore, independent of renal function. This implies that patients with chronic renal failure are not at an increased risk for accumulation of the element, compared with patients with normal renal function. In animal studies, no adverse effects on bone were seen in healthy animals receiving Lanthanum carbonate. In 5/6th nephrectomized rats, very high doses of Lanthanum (1000-2000 mg/kg) affected bone mineralization. This was not due to a direct toxic effect on bone, but was secondary to phosphate depletion induced by Lanthanum and, as with any gastro-intestinal phosphate-binding agent, can be reversed with a phosphate-supplemented diet. In a phase III clinical trial, bone biopsies were taken from dialysis patients at baseline and after 1 year of treatment with either Lanthanum carbonate (median dose, 1250 mg/day) or calcium carbonate (median dose, 2000 mg/day). Patients treated with Lanthanum carbonate for 1 year did not experience any of the aluminium-like toxic effects on bone expressed as either osteomalacia or adynamic bone disease.
Ronny Blust - One of the best experts on this subject based on the ideXlab platform.
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Use of Lanthanum for water treatment A matter of concern
Chemosphere, 2019Co-Authors: Geert J. Behets, Kayawe Valentine Mubiana, Ludwig V. Lamberts, Karin Finsterle, Nigel Traill, Ronny Blust, Patrick C. D'haeseAbstract:Abstract Among several other eutrophication management tools, Phoslock®, a Lanthanum modified bentonite (LMB) clay, is now frequently used. Concerns have been raised as to whether exposure to Phoslock®-treated water may lead to Lanthanum accumulation/toxicity in both animals and humans. In the present experimental study, rats were administered Lanthanum orally as either Lanthanum carbonate, Lanthanum chloride or Phoslock® at doses of either 0.5 or 17 mg/L during 10 weeks. Controls received vehicle. The gastrointestinal absorption and tissue distribution of Lanthanum was investigated. Extremely strict measures were implemented to avoid cross-contamination between different tissues or animals. Results showed no differences in gastrointestinal absorption between the different compounds under study as reflected by the serum Lanthanum levels and concentrations found in the brain, bone, heart, spleen, lung, kidney and testes. At sacrifice, significant but equally increased Lanthanum concentrations versus vehicle were observed in the liver for the highest dose of each compound which however, remained several orders of magnitude below the liver Lanthanum concentration previously measured after long-term therapeutic administration of Lanthanum carbonate and for which no hepatotoxicity was noticed in humans. In conclusion, (i) the use of LMB does not pose a toxicity risk (ii) gastrointestinal absorption of Lanthanum is minimal and independent on the type of the compound, (iii) with exception of the liver, no significant increase in Lanthanum levels is observed in the various organs under study, (iv) based on previous studies, the slightly increased liver Lanthanum levels observed in a worst case scenario do not hold any risk of hepatotoxicity.
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hepatocellular transport and gastrointestinal absorption of Lanthanum in chronic renal failure
Kidney International, 2009Co-Authors: An R. Bervoets, Stephen J.p. Damment, Geert J. Behets, Steven C. Verberckmoes, D Schryvers, Frank Roels, Zhang Yang, Simonne Dauwe, Valentine K Mubiana, Ronny BlustAbstract:Lanthanum carbonate is a new phosphate binder that is poorly absorbed from the gastrointestinal tract and eliminated largely by the liver. After oral treatment, we and others had noticed 2–3 fold higher Lanthanum levels in the livers of rats with chronic renal failure compared to rats with normal renal function. Here we studied the kinetics and tissue distribution, absorption, and subcellular localization of Lanthanum in the liver using transmission electron microscopy, electron energy loss spectrometry, and X-ray fluoresence. We found that in the liver Lanthanum was located in lysosomes and in the biliary canal but not in any other cellular organelles. This suggests that Lanthanum is transported and eliminated by the liver via a transcellular, endosomal-lysosomal-biliary canicular transport route. Feeding rats with chronic renal failure orally with Lanthanum resulted in a doubling of the liver levels compared to rats with normal renal function, but the serum levels were similar in both animal groups. These levels plateaued after 6 weeks at a concentration below 3 μg/g in both groups. When Lanthanum was administered intravenously, thereby bypassing the gastrointestinal tract-portal vein pathway, no difference in liver levels was found between rats with and without renal failure. This suggests that there is an increased gastrointestinal permeability or absorption of oral Lanthanum in uremia. Lanthanum levels in the brain and heart fluctuated near its detection limit with long-term treatment (20 weeks) having no effect on organ weight, liver enzyme activities, or liver histology. We suggest that the kinetics of Lanthanum in the liver are consistent with a transcellular transport pathway, with higher levels in the liver of uremic rats due to higher intestinal absorption.
Marc E. De Broe - One of the best experts on this subject based on the ideXlab platform.
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demonstration of Lanthanum in liver cells by energy dispersive x ray spectroscopy electron energy loss spectroscopy and high resolution transmission electron microscopy
Journal of Microscopy, 2006Co-Authors: Zhiqing Yang, Patrick C Dhaese, D Schryvers, Frank Roels, Marc E. De BroeAbstract:The appearance of Lanthanum in liver cells as a result of the injection of Lanthanum chloride into rats is investigated by advanced transmission electron microscopy techniques, including electron energy loss spectroscopy and high-resolution transmission electron microscopy. It is demonstrated that the lysosomes contain large amounts of Lanthanum appearing in a granular form with particle dimensions between 5 and 25 nm, whereas no Lanthanum could be detected in other surrounding cellular components.
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Lanthanum a safe phosphate binder
Seminars in Dialysis, 2006Co-Authors: Veerle P. Persy, Marc E. De Broe, Geert J. Behets, An R. Bervoets, Patrick C DhaeseAbstract:: Accumulation of inorganic phosphate due to renal functional impairment contributes to the increased cardiovascular mortality observed in dialysis patients. Phosphate plays a causative role in the development of vascular calcification in renal failure; treatment with calcium-based phosphate binders and vitamin D can further increase the Ca x PO(4) product and add to the risk of ectopic mineralization. The new generation of calcium-free phosphate binders, sevelamer and Lanthanum, can control hyperphosphatemia without adding to the patients calcium load. In this article, the metabolism of Lanthanum carbonate and its effects in bone, liver and brain are discussed. Although Lanthanum is a metal cation its effects are not comparable to those of aluminum. Indeed, in clinical studies no toxic effects of Lanthanum have been reported after up to four years of follow-up. The bioavailability of Lanthanum is extremely low. The effects observed in bone are due to phosphate depletion, with no signs of direct bone toxicity yet observed in rats or humans. The liver is the main route of excretion for Lanthanum carbonate, which can be localized in the lysosomes of hepatocytes. No Lanthanum could be detected in brain tissue.
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Localization of Lanthanum in bone of chronic renal failure rats after oral dosing with Lanthanum carbonate
Kidney International, 2005Co-Authors: Geert J. Behets, Marc E. De Broe, Steven C. Verberckmoes, Line Oste, An R. Bervoets, Murielle Salomé, Alan G. Cox, John Denton, Patrick C. D'haeseAbstract:Localization of Lanthanum in bone of chronic renal failure rats after oral dosing with Lanthanum carbonate. Background Lanthanum carbonate has been shown to be a safe, effective phosphate-binding agent. We have shown that an impaired mineralization in chronic renal failure rats treated with high doses of Lanthanum carbonate develops secondary to phosphate depletion and is therefore pharmacologically mediated rather than a direct effect of Lanthanum on bone. Although bulk bone Lanthanum concentrations are low, it is important to consider the localization within a given tissue. Methods Using the scanning x-ray micro-fluorescence set-up at beamline ID21 of the European Synchrotron Radiation Facility, calcium and Lanthanum distributions in bone samples were mapped. Results In chronic renal failure rats loaded orally with Lanthanum carbonate (12 weeks) (2000 mg/kg/day), bulk bone Lanthanum concentrations reached values up to 5 μg/g wet weight. Lanthanum could be demonstrated at the edge of the mineralized bone, at both actively mineralizing and quiescent sites, independent of the type of bone turnover. In the presence of hyperparathyroid bone disease, Lanthanum was also distributed throughout the mineralized trabecular bone. No correlation with the presence of osteoid, or the underlying bone pathology could be demonstrated. After a 2- or 4-week washout period before sacrifice, Lanthanum localization did not change significantly. Conclusion The comparable localization of Lanthanum in different types of bone turnover, and the unchanged localization after washout and consequent disappearance of the mineralization defect, indicates no relationship between the localization of Lanthanum in bone and the presence of a mineralization defect.
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Improving outcomes in hyperphosphataemia.
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2004Co-Authors: Marc E. De Broe, Patrick C. D'haeseAbstract:Preclinical studies have shown that Lanthanum has a very high phosphate-binding capacity at gastrointestinal pH, while clinical trials have shown Lanthanum carbonate to be an effective, well-tolerated phosphate binder for the treatment of hyperphosphataemia in patients with end-stage renal disease. Optimization of bone health is an important issue in these patients, and, based on theoretical grounds, there have been concerns that Lanthanum will have toxic effects on bone similar to those of aluminium. However, compared with aluminium, absorption of Lanthanum is extremely low and Lanthanum treatment is not associated with systemic toxicity. In addition, unlike aluminium, elimination of Lanthanum is not through the kidney, but mainly takes place via the biliary route and is, therefore, independent of renal function. This implies that patients with chronic renal failure are not at an increased risk for accumulation of the element, compared with patients with normal renal function. In animal studies, no adverse effects on bone were seen in healthy animals receiving Lanthanum carbonate. In 5/6th nephrectomized rats, very high doses of Lanthanum (1000-2000 mg/kg) affected bone mineralization. This was not due to a direct toxic effect on bone, but was secondary to phosphate depletion induced by Lanthanum and, as with any gastro-intestinal phosphate-binding agent, can be reversed with a phosphate-supplemented diet. In a phase III clinical trial, bone biopsies were taken from dialysis patients at baseline and after 1 year of treatment with either Lanthanum carbonate (median dose, 1250 mg/day) or calcium carbonate (median dose, 2000 mg/day). Patients treated with Lanthanum carbonate for 1 year did not experience any of the aluminium-like toxic effects on bone expressed as either osteomalacia or adynamic bone disease.
Stephen J.p. Damment - One of the best experts on this subject based on the ideXlab platform.
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hepatocellular transport and gastrointestinal absorption of Lanthanum in chronic renal failure
Kidney International, 2009Co-Authors: An R. Bervoets, Stephen J.p. Damment, Geert J. Behets, Steven C. Verberckmoes, D Schryvers, Frank Roels, Zhang Yang, Simonne Dauwe, Valentine K Mubiana, Ronny BlustAbstract:Lanthanum carbonate is a new phosphate binder that is poorly absorbed from the gastrointestinal tract and eliminated largely by the liver. After oral treatment, we and others had noticed 2–3 fold higher Lanthanum levels in the livers of rats with chronic renal failure compared to rats with normal renal function. Here we studied the kinetics and tissue distribution, absorption, and subcellular localization of Lanthanum in the liver using transmission electron microscopy, electron energy loss spectrometry, and X-ray fluoresence. We found that in the liver Lanthanum was located in lysosomes and in the biliary canal but not in any other cellular organelles. This suggests that Lanthanum is transported and eliminated by the liver via a transcellular, endosomal-lysosomal-biliary canicular transport route. Feeding rats with chronic renal failure orally with Lanthanum resulted in a doubling of the liver levels compared to rats with normal renal function, but the serum levels were similar in both animal groups. These levels plateaued after 6 weeks at a concentration below 3 μg/g in both groups. When Lanthanum was administered intravenously, thereby bypassing the gastrointestinal tract-portal vein pathway, no difference in liver levels was found between rats with and without renal failure. This suggests that there is an increased gastrointestinal permeability or absorption of oral Lanthanum in uremia. Lanthanum levels in the brain and heart fluctuated near its detection limit with long-term treatment (20 weeks) having no effect on organ weight, liver enzyme activities, or liver histology. We suggest that the kinetics of Lanthanum in the liver are consistent with a transcellular transport pathway, with higher levels in the liver of uremic rats due to higher intestinal absorption.
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A Model of the Kinetics of Lanthanum in Human Bone, Using Data Collected during the Clinical Development of the Phosphate Binder Lanthanum Carbonate
Clinical Pharmacokinetics, 2008Co-Authors: Felix Bronner, Michael Pennick, Boris M Slepchenko, Stephen J.p. DammentAbstract:Objective: Lanthanum carbonate (Fosrenol®) is a non-calcium phosphate binder that controls hyperphosphataemia without increasing calcium intake above guideline targets. The biological fate and bone load of Lanthanum were modelled with the aid of a four-compartment kinetic model, analogous to that of calcium. Methods: The model used data from healthy subjects who received intravenous Lanthanum chloride or oral Lanthanum carbonate, and bone Lanthanum concentration data collected from dialysis patients during three long-term trials (up to 5 years). Results: Infusion of Lanthanum chloride or ingestion of Lanthanum carbonate led to a rapid rise in plasma Lanthanum concentrations, followed by an exponential decrease. Comparison of oral and intravenous exposure confirmed that Lanthanum is very poorly absorbed. On a typical intake of Lanthanum (3000 mg/day as Lanthanum carbonate), the rate of absorption was calculated as 2.2 μg/h, with a urinary excretion rate constant of 0.004—0.01 h^−1. The faecal content of endogenous Lanthanum was estimated to be 8- to 20-fold greater than that of urine, compared with a ratio of only about 1 for calcium. The model predicts that upon multiple dosing, plasma Lanthanum concentrations rise rapidly to a near plateau and then increase by about 3% per year. However, this small change is obscured by the variability of the study data, which show that a plateau is rapidly attained by 2 weeks and is thereafter maintained for at least 2 years. The initial deposition rate of Lanthanum in bone was 1 μg/g/year and, after 10 years of Lanthanum carbonate treatment, the model predicts a 7-fold increase in total bone Lanthanum (from 10 mg to 69 mg [from 1 μg/g wet weight to 6.6 μg/g wet weight]), with Lanthanum cleared after cessation of treatment at 13% per year. The model indicates that Lanthanum flow from bone surface to bone interior is much lower than that of calcium. Conclusion: Bone is the major reservoir for metals, but bone Lanthanum concentrations are predicted to remain low after long-term treatment because of very poor intestinal absorption.
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Systemic Lanthanum is excreted in the bile of rats.
Toxicology letters, 2007Co-Authors: Stephen J.p. Damment, Michael PennickAbstract: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
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Absolute bioavailability and disposition of Lanthanum in healthy human subjects administered Lanthanum carbonate.
Journal of clinical pharmacology, 2006Co-Authors: Michael Pennick, Kerry Dennis, Stephen J.p. DammentAbstract:Lanthanum carbonate [La2(CO3)3] is a noncalcium, non-aluminum 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 microg elemental Lanthanum over a 4-hour period), a single 1-g oral dose [chewable La2(CO3)3 tablets; 4 x 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 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.
