Lanthanum carbonate

Controlling hyperphosphatemia in patients with chronic renal failure on renal dialysis is a major problem. None of the available calcium- or aluminum-based phosphate binders match the requirements for an ideal agent, each having its own limitations. The introduction of sevelamer hydrochloride represented a step change in management. Lanthanum carbonate is an alternative nonaluminium, noncalcium phosphate binder. Taken with food, it is well tolerated. It is poorly absorbed and does not require functioning kidneys to be removed from the body. There is no evidence from current studies that it accumulates to biologically significant levels in tissues, but despite the large numbers of patients included in clinical trials, experience with long-term dosing is limited and, as with every new drug used in this type of clinical setting, patients should be carefully monitored as experience with the drug increases. Lanthanum carbonate binds phosphate effectively across the physiological pH range of the upper gastrointestinal tract, and has no detrimental effect on calcium, vitamin D or parathyroid hormone metabolism. From the extensive trial data it seems that lanthanum carbonate is an effective and practical phosphate binder. Lanthanum carbonate and sevelamer are two new oral phosphate binding agents that with others currently in preclinical trials, such as stabilized polynuclear iron idroxide, could well represent a significant breakthrough in the management of hyperphosphatemia in patients with chronic renal failure in whom dietary phosphate restriction and cheaper oral phosphate binding agents prove unsatisfactory. Comparative trials and enhanced clinical experience are needed before the exact place of these competing and complementary therapies can be properly identified in patient management.     

Lanthanum carbonate (Shire)

Shire Pharmaceuticals Group plc, under exclusive license from AnorMED Inc (a subsidiary of Johnson Matthey), is developing lanthanum carbonate, a phosphate-binding lanthanum salt, for the potential treatment of hyperphosphatemia in dialysis patients. It is currently in pre-registration in the US, Canada and Western Europe, and earlier stage clinical trials are ongoing in Japan.     

Clinical consequences and novel therapy of hyperphosphatemia: Lanthanum carbonate for dialysis patients

Vascular calcification is a very common event in patients affected by diabetes and chronic kidney disease (CKD). Recently, it has been well documented that abnormalities in mineral and bone metabolism in CKD patients associate with increased morbidity and mortality. Elevated serum phosphate and calcium-phosphate product levels play an important role in the pathogenesis of vascular mineralization in uremic patients and also appear to be associated with increased cardiovascular mortality. Together with classical passive precipitation of calcium-phosphate in soft tissues, during the last decade it has been demonstrated that inorganic phosphate may cause extraskeletal calcification directly through a real "ossification" of the tunica media in the vasculature of CKD patients. Therefore, control of phosphate retention is now an even more crucial target of treatment in patients affected by chronic kidney disease. The "classical" treatment of secondary hyperparathyroidism and hyperphosphatemia in CKD patients consists of either calcium or aluminium based phosphate-binders and calcitriol administration. Unfortunately, this "old generation" therapy is not free of complications. Patents are also reported discussing the role of derivatives of Lanthanum carbonate hydrates are also used for the treatment of hyperphosphataemia in patients with renal failure. New calcium- and aluminium-free phosphate binders, such as sevelamer hydrochloride and lanthanum carbonate, can be used to treat hyperphosphatemia and secondary hyperparathyroidism, reduce atherosclerotic process, and prevent vascular calcification in CKD patients.     

Lanthanum carbonate for the treatment of hyperphosphataemia in renal failure and dialysis patients

Hyperphosphataemia is a usual accompaniment of end stage renal disease and dialysis, in the absence of dietary phosphate restriction or supplemental phosphate binders. It is associated with renal osteodystrophy, metastatic calcification and increased mortality and morbidity. Despite dietary restriction and dialysis, most patients will require a phosphate-binding agent to treat this condition. However, phosphate control has not significantly improved over the last two decades, mainly because of the lack of an ideal oral phosphate-binding agent. Aluminium- and calcium-based agents are associated with major side effects, despite their undoubted efficacy. Although sevel-amer hydrochloride represents a step forward in the management of hyperphosphataemia, it is not an ideal phosphate binder due to its cost and tablet burden. Lanthanum carbonate is the most recent non-calcium, non-aluminium, phosphate-binding agent. It is effective and well-tolerated, and no negative effects on bone histology have been observed.     

Lanthanum carbonate for the treatment of hyperphosphataemia in renal failure and dialysis patients

Hyperphosphataemia is a usual accompaniment of end stage renal disease and dialysis, in the absence of dietary phosphate restriction or supplemental phosphate binders. It is associated with renal osteodystrophy, metastatic calcification and increased mortality and morbidity. Despite dietary restriction and dialysis, most patients will require a phosphate-binding agent to treat this condition. However, phosphate control has not significantly improved over the last two decades, mainly because of the lack of an ideal oral phosphate-binding agent. Aluminium- and calcium-based agents are associated with major side effects, despite their undoubted efficacy. Although sevel-amer hydrochloride represents a step forward in the management of hyperphosphataemia, it is not an ideal phosphate binder due to its cost and tablet burden. Lanthanum carbonate is the most recent non-calcium, non-aluminium, phosphate-binding agent. It is effective and well-tolerated, and no n-egative effects on bone histology have been observed.     

分光光度法测定碳酸镧咀嚼片中镧含量

目的：以偶氮胂Ⅲ为显色剂,氯乙酸-氢氧化钠为缓冲溶液,用分光光度法直接测定碳酸镧咀嚼片中镧含量。方法：最佳的显色酸度为pH2．8-3．0,最佳测定波长为656nm．结果：镧含量在0．3—3．0μg／mL范围内与吸光度呈现良好的线性关系,线性回归方程为Y=0．3381X-0．0215,相关系数r=0．9998。回收率为98．7％-99．6％。结论：本法显色稳定性好,灵敏度高,操作简便,快速。     

Activation of carboplatin by carbonate

Carboplatin, [Pt(NH3)2(CBDCA-O,O')], 1, where CBDCA is cyclobutane-1,1-dicarboxylate, is in wide clinical use for the treatment of ovarian, lung, and other types of cancer. Because carboplatin is relatively unreactive toward nucleophiles, an important question concerning the drug is the mechanism by which it is activated in vivo. Using [1H,15N] heteronuclear single quantum coherance spectroscopy (HSQC) NMR and 15N-labeled carboplatin, we show that carboplatin reacts with carbonate ion in carbonate buffer to produce ring-opened products, the nature of which depends on the pH of the medium. The assignment of HSQC NMR resonances was facilitated by studying the reaction of carboplatin in strong acid, which also produces a ring-opened product. The HSQC NMR spectra and UV-visible difference spectra show that reaction of carboplatin with carbonate at pH > 8.6 produces mainly cis-[Pt(NH3)2(CO3(-2))(CBDCA-O)]-2, 5, which contains the mono-dentate CBDCA ligand and mono-dentate carbonate. At pH 6.7, the primary product is the corresponding bicarbonato complex, which may be in equilibrium with its decarboxylated hydroxo analogue. The UV-visible absorption data indicate that the pKb for the protonation of 5 is approximately 8.6. Thus, the reaction of carboplatin with carbonate produces a mixture of ring-opened species that are anions at physiological pH. HSQC NMR studies on 15N-labeled carboplatin in RPMI culture media containing 10% fetal bovine serum with and without added carbonate suggest that carbonate is the attacking nucleophile in culture media. However, because the rate of reaction of carbonate with carboplatin at physiological pH is small, NMR peaks for ring-opened carboplatin were not detected with HSQC NMR. The rate of disappearance of carboplatin in culture medium containing 9 x 10(8) Jurkat cells is essentially the same as that in carbonate buffer, indicating that the ring-opening reaction is not affected by the presence of cells. This work shows that carbonate at concentrations found in culture media, blood, and the cytosol readily displaces one arm of the CBDCA ligand of carboplatin to give a ring-opened product, which at physiological pH is a mixture of anions. These ring-opened species may be important in the uptake, antitumor properties, and toxicity of carboplatin.     

Organic reactions utilizing cycilic carbonate

The polymerization of title compound (MCEC, I) with phenols led to give corresponding resole type polymer. Phenol and p-methoxyphenol polymer had a relative higher molecular weight and a property of elastomer, but p-chloro- and p-nitrophenol polymer had a lower ones. Also, phenol and p-methoxyphenol gave to crosslinking polymer by elongation of reaction period and raising of temperature.     

碳酸司维拉姆联合小剂量碳酸钙治疗尿毒症高磷血症的研究

目的:分析对尿毒症高磷血症行以碳酸司维拉姆联合小剂量碳酸钙治疗的临床效果。方法:从2018年6月~2019年1月择取54例尿毒症高磷血症患者,随机分成两组。对照组27例行以碳酸钙治疗,研究组27例行以碳酸司维拉姆联合小剂量碳酸钙治疗,对照分析两组临床效果。结果:从矿物质骨代谢指标来看,治疗前钙、磷、钙磷乘积、ALP以及iPTH对比无显著差异,治疗后研究组钙、磷、钙磷乘积均优于对照组,P<0.05,ALP以及iPTH组间无显著差异,P>0.05;从脂代谢指标来看,治疗前两组TC、TG、LDL-C、HLD-C对比无显著差异,治疗后研究组LDL-C、HLD-C均优于对照组,P<0.05,TC、TG组间无显著差异,P>0.05;从肾功能指标来看,治疗前两组Cr、BUN对比无显著差异,治疗后研究组Cr、BUN均优于对照组,P<0.05。结论:对尿毒症高磷血症行以碳酸司维拉姆联合小剂量碳酸钙治疗的临床效果确切,不仅可以使矿物质骨代谢指标得到改善,还可以使脂代谢指标以及肾功能指标得到改善,临床价值显著。     

Lanthanum chloride promotes mitochondrial apoptotic pathway in primary cultured rat astrocytes

Population surveys and animal experiments have shown that rare earth elements (REEs) cause neurological defects. However, the detailed mechanisms underlying these effects are still unclear. Given that lanthanum is commonly used for investigating into REEs‐induced neurological defects, this study chose lanthanum chloride (LaCl₃) to show that LaCl₃ promotes mitochondrial apoptotic pathway in primary cultured rat astrocytes by regulating expression of Bcl‐2 family proteins. The main findings of this study are (1) LaCl₃ treatment (0.25, 0.5, and 1.0 mM for 12–48 h) induced the astrocytes damages with a concentration‐dependent manner, which were confirmed with methyl thiazolyl tetrazolium and lactate dehydrogenase release assays, and morphological examination. (2) A 24 h treatment of LaCl₃ concentration‐dependently decreased mitochondrial membrane potential, increased cytochrome c release from mitochondria into cytosol, elevated caspase 9 and 3 expression, and promoted astrocyte apoptosis. (3) LaCl₃ treatment increased the ratio of pro‐apoptotic Bax and antiapoptotic Bcl‐2 proteins, which in turn broke the balance among pro‐apoptotic and antiapoptotic Bcl‐2 family proteins, leading to astrocyte apoptosis. Our results indicate that LaCl₃ alters Bcl‐2 family protein expressions, which in turn promote mitochondrial apoptotic pathway, and thus astrocytic damage. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 489–497, 2013.     

Pharmacokinetics of lithium carbonate in children

The pharmacokinetics in both serum and saliva of a single oral dose of lithium carbonate 300 mg was investigated in nine children aged 9 to 12 years. The serum and saliva concentration-time curves were parallel and biexponential, with a fast distribution phase after the peak at the second hour and a slow elimination phase starting from the 12th hour. The fast phase half-life was 6.0 +/- 1.8 hour in the serum, and 5.8 +/- 1.9 hour in the saliva. The slow phase half-life was 17.9 +/- 7.4 hour in the serum and 15.6 +/- 8.2 hour in the saliva. Lithium was 2.84 +/- 0.86 times higher in the saliva than in the serum, with a saliva/serum r coefficient of correlation of 0.93. A relatively large error was found in predicting serum levels from saliva. There were significant intersubject differences in the saliva/serum ratio, which point to the need for individual ratios in clinical use. On the whole, the pharmacokinetics of lithium in children had the same features as in adults, with a trend toward a shorter elimination half-life and higher total clearance.     

Comparative Evaluation of the In Vitro Efficacy of Lanthanum Carbonate Chewable Tablets

The aims of this study were to systematically evaluate the effects of pH levels, phosphate concentrations, and tablet integrity on the phosphate binding profiles of lanthanum carbonate chewable tablets, and to compare the in vitro phosphate binding efficacy of one reference and two test products of lanthanum carbonate chewable tablets. Langmuir equation was utilized to calculate the binding constants k₁ and k₂. The phosphate binding to the tablets of lanthanum carbonate product was pH dependent, with a faster binding rate at low pH. The crushed tablets bind phosphate more rapid. Compared with the whole tablets, the kinetic binding profiles from the crushed tablets were less variable under all conditions for both test and reference products. The phosphate level has a significant impact on the phosphate binding for both whole and crushed tablets under all pH conditions, with more binding at higher phosphate concentration. The phosphate binding profiles displayed significant difference among the products. For a crushed tablet, the phosphate binding to lanthanum reached equilibrium within 8 h under all conditions. The 90% confidence interval for the k₂ ratio (test/ reference) was well within the 80%–125% under all pH conditions. However, the k ratio varies from 54% to 144%.     

N-取代四氮杂大环镧(Ⅲ)配合物的合成及其生物活性

合成了2,2,4,9,9,11-六甲基-N1、N3-二乙酸四氮杂十四烷大环(A)和2,2,4,9,9,11-六甲基-N1、N3-二对甲基苯磺酰基四氮杂十四烷大环(B)以及它们的镧配合物,用元素分析、摩尔电导、IR和1H-NMR谱等手段表征了这些化合物的结构。初步生物活性表明,各化合物均有较强的抗肿瘤活性。