Pharmacokinetics of CaNa 2 EDTA and chelation of lead in renal failure

The pharmacokinetics of 1 gm intramuscular doses of CaNa 2 ( 14 C‐)EDTA and the chelation of lead (Pb) were studied in 10 subjects with varying degrees of renal function and normal body burdens of Pb. The clearance of CaNa 2 EDTA significantly correlated with creatinine clearances (CL CR ) (r = 0.8373; P = 0.0097). Clearances were decreased in subjects with CL CR < 70 ml/min as compared with subjects with CLCR > 100 ml/min (28 vs. 76 ml/min). Maximum serum CaNa 2 EDTA concentrations and volume of distribution (V area ) (0.05 to 0.23 L/kg) were similar in all subjects. The V area is smaller than previously described and is more consistent with other experimental data. Considering all subjects, initial blood Pb concentrations correlated with cumulative urine Pb excretion over 3 days (r = 0.8967; P = 0.0005). Urine Pb excretion did not correlate with measures of renal function or measures of CaNa 2 EDTA kinetics. Subjects with abnormal CL CR showed significantly greater decreases in blood Pb from day 1 to day 4 (7.0 µg/dl vs. 1.2 µg/dl) compared with normal subjects. These decreases in blood Pb correlated with CL CR (r = 0.7774; P = 0.138) and urine protein (r = 0.8435; P = 0.0087) but not with urine Pb excretion. Renal dysfunction may alter Pb chelatability, bone‐blood Pb reequilibration, PbEDTA distribution, or PbEDTA excretion. Clinical Pharmacology and Therapeutics (1986) 40 , 686–693; doi: 10.1038/clpt.1986.245