Lead, chelates

Gill F Children s Hospital of Philadelphia, Philadelphia, PA To evaluate the effect of lead chelation in conjunction with consumption of multivitamins and minerals on developmental status (humans) National Center for Research Resources... 

Renal function Adequately hydrate all patients undergoing treatment. Exercise caution in using succimer therapy in patients with compromised renal function. Limited data suggest that succimer is dialyzable but that the lead chelates are not. Hepatic function Trans ent mild elevations of serum transaminases have been observed in 6% to 10% of patients during the course of therapy. Monitor serum transaminases before the start of therapy and at least weekly during therapy. 

The longer the half-life of a metal in a particular organ, the less effectively it will be removed by chelation. For example, in the case of lead chelation with calcium EDTA or succimer, or of plutonium chelation with DTPA, the metal is more effectively removed from soft tissues than from bone, where incorporation into bone matrix results in prolonged retention. 

Liquid chromatography-absorption spectrophotometry was used by Vlacil and Hamplova [281] for the determination of lead and copper in natural waters. The metal diethyldithiocarbamates are extracted and concentrated by evaporation, followed by reversed phase liquid chromatography of the chelates. The copper and lead chelates can also be sequentially detected by spectrophotometry at 440 and 280nm. The detection limits for copper and lead were 8.6 and 17pg L 1 respectively, when liquid chromatography was used, and were 58 and 17pg L respectively when spectrophotometry was used. 

Sodium calciumedetate is the calcium chelate of the disodium salt of ethylenediaminetetra-acetic acid (calcium EDTA). It is effective in acute lead poisoning because of its capacity to exchange calcium for lead the lead chelate is excreted in the urine, leaving behind a harmless amount of calcium. Dimercaprol may usefully be combined with sodium calciumedetate when lead poisoning is severe, e.g. with encephalopathy. 

Succimer is the meso isomer of 2,3-dimethylmercapto-succinic acid (DMSA). It is used as a lead chelator for oral administration (1). Nausea, vomiting, diarrhea, and anorexia are common. Rashes, sometimes necessitating withdrawal, have been reported in up to 10% of adults and 5% of children, and mild transient rises in serum transaminase activity in 6-10% (mostly adults) (2,3). Life-threatening hyperthermia occurred on two occasions in one subject, but no details were given. Iron can be safely and effectively given to patients taking succimer, which (unlike dimercaprol) does not appear to deplete iron stores or to form a toxic chelate that would preclude the parenteral administration of iron (3). 

Mann KV, Travers JD. Succimer, an oral lead chelator. Clin Pharm 1991 10(12) 914-22. 

Ca2+) from EDTA in accordance with its 107-fold greater affinity for the chelate. Free lead ions are removed from the blood and tissues (directly from bone and indirectly from parenchymatous organs) as the soluble lead chelate formed is rapidly excreted by glomerular filtration. Because of its ionic character, it is unlikely that CaNa2EDTA significantly penetrates cells the apparent volume of distribution is numerically similar to the extracellular fluid volume. 

The EDTA test is performed in adults by parenteral administration of 1 to 3 g of CaNa2EDTA over 4 to 12 hours with subsequent collection of 24-hour urine samples over 1 to 4 days. A dose of 20 to 30 mg EDTA/ kg is generally used in children. Adults without undue prior lead absorption excrete up to 650 pg of lead-chelate in the mine. Neither fhe dose (1 to 3 g) nor the route of adminisfration (intravenous or intramuscular) appears to critically modify the normal response to chelation testing [70, 71], but in the presence of renal fadme (serum creatinine greater fhan 1.5 mg/ dl) mine collections should be extended to at least 3 days. The adequacy of coUecfion can be checked by simultaneous measurement of creatinine excretion (1.3 g of creatinine/ day is an acceptable lower limit in normal adult males). 

Succimer is the first orally active lead chelator available for children, with a safety and efhcacy profile that surpasses that of D-penicillamine. Succimer usually is given every... 

Succimer produces a lead diuresis with a subsequent lowering of blood lead levels and attenuation of the untoward biochemical effects of lead, manifested by normalization of 5-ALA dehydrase activity. The succimer-lead chelate also is eliminated in bile the fraction eliminated undergoes enterohepatic circulation. 

Chelation therapy often is begun with dimercaprol (3—4 mg/kg intramuscularly every 4—12 hours) until abdominal symptoms subside and charcoal (if given initially) is passed in the feces. Oral treatment with penicillamine then may be substituted for dimercaprol and continued for 4 days. Penicillamine is given in 4 divided doses to a maximum of 2 g/day. If symptoms recur after cessation of chelation therapy, a second course of penicillamine may be instituted. Succimer (2,3-dimercaptosuccinic acid), a derivative of dimercaprol, is efficacious in the treatment of arsenic poisoning but is FDA-approved only for lead chelation in children. 

Mechanisms and Rates of Lead-Chelate Dissociation and Substitution Reactions... 

C. Urinary lead excretion increases and decreases more rapidly than blood lead. Normal urinary lead excretion is less than 50 mcg/day. Several empiric protocols that measure 6- or 24-hour urinary lead excretion after calcium EDTA challenge have been developed to identify persons with elevated body lead burdens. However, since chelatable lead predominantly reflects lead in soft tissues, which in most cases already correlates satisfactorily with blood lead, chelation challenges are seldom indicated in clinical practice. 

A 65-year old man with chronic obstructive airways disease and chronic lead intoxication was given a 19-day course of lead chelation with succimer. His theophylline level was found to be reduced from about 11 mg/L to 7 mg/L on day 6 and remained at this level until about 9 days after the course of succimer was completed, when it returned to pretreatment levels. His clinical status did not alter despite these changes possibly because he was also taking prednisone. The reason for these alterations is not understood. 

Mean BLL in workers = 32 fig/dL tibia lead, chelatable lead also measured... 

Lin, J.-L., Kim, R., Tsaih, S.-W., Sparrow, D., Hu, H., 2001. Lead chelation therapy and urate excretion in patients with chronic kidney diseases and gout. Kidney Int. 60,... 

The use of iron chelators has been reviewed [3 ] and some articles have provided a practical summary comparison of today s leading chelating drugs [4 , 5 ] (see Table 1). The use of combinations of these drugs may lessen some problems or create others [SEDA 31, 399]. 

Lead Chelation, then atomic absorption spectrometry (AAS) 0.2 pg/ml [48]... 

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