Pharmacokinetics of CaNa2EDTA and chelation of lead in renal failure

The pharmacokinetics of 1 gm intramuscular doses of CaNa2 (14C-)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 CaNa2EDTA significantly correlated with creatinine clearances (CLCR) (r = 0.8373; P = 0.0097). Clearances were decreased in subjects with CLCR less than 70 ml/min as compared with subjects with CLCR greater than 100 ml/min (28 vs. 76 ml/min). Maximum serum CaNa2EDTA concentrations and volume of distribution (Varea) (0.05 to 0.23 L/kg) were similar in all subjects. The Varea 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 CaNa2EDTA kinetics. Subjects with abnormal CLCR showed significantly greater decreases in blood Pb from day 1 to day 4 (7.0 micrograms/dl vs. 1.2 micrograms/dl) compared with normal subjects. These decreases in blood Pb correlated with CLCR (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.