B. C. Campbell

The effects of industrial lead poisoning on cytochrome P450 mediated phenazone (antipyrine) hydroxylation.

SummaryIn a group of ten male adults admitted to hospital with clinical symptoms of lead exposure, phenazone elimination rates, blood δ-amino-laevulinic acid dehydratase (ALA.D) activity, blood lead levels and haemoglobin were measured. Investigations were carried out before, immediately after and again at least 12 weeks after cessation of CaEDTA (sodium calcium edetate) chelation therapy. Following chelation, phenazone elimination rates were increased as assessed by a decrease in half life and increase in clearance. This was significant, both immediately after and 12 weeks after cessation of chelation therapy. The change in rate of phenazone metabolism was associated with improved clinical status, with lowered blood lead levels and raised haemoglobin and ALA.D activity. The results of the study suggest that the depression in phenazone elimination in lead intoxication is possibly due to depressed hepatic cytochrome P450 levels.

Lead exposure and renal failure: Does renal insufficiency influence lead kinetics?

Blood and urine lead concentrations have been measured in 40 subjects with normal and impaired renal function. Derived renal lead clearance varied widely, but was not influenced by the degree of renal impairment. Lead, however, appeared to reduce its own clearance. These findings provide additional evidence of nephrotoxicity from sub-clinical lead exposure.

Changes in serum aluminium, blood zinc, blood lead and erythrocyte δ-aminolaevulinic acid dehydratase activity during haemodialysis

Abstract In a study of 18 patients on haemodialysis, erythrocyte δ-aminolaevulinic acid dehydratase (ALAD), serum aluminium, blood zinc and blood lead concentrations were increased significantly following haemodialysis. The increase in erythrocyte ALAD activity was found to be significantly linearly correlated with the increase in blood zinc concentrations. In comparison with control subjects, the patients had significantly lower activities of ALAD and significantly increased serum aluminium concentrations. When zinc and lead concentrations were corrected for packed cell volume they were found to be significantly higher in the patient group than in the control group.

Kinetics of lead following intravenous administration in man

Whole body retention of lead (Pb) and lead kinetics in blood, urine and faeces were determined over 2 weeks following i.v. administration of 203Pb-labelled chloride to 2 subjects. Pb was retained with a biological half-life of 73 days (mean). After day 1 Pb excreted in urine and faeces remained fairly constant at 1% and 0.3% of administered dose, respectively. There was a daily loss of 0.5% by other routes. There was a rapid clearance of isotope from plasma with a half-life of 1 min (mean). At 60 min 45% of the administered dose was in erythrocytes; this changed little over the 2 weeks.

The influence of protein binding on disopyramide clearance

SummaryIndividual disopyramide clearance is not constant and previous studies have suggested that this may be time and/or concentration dependent. Steady state disopyramide concentrations were achieved in six volunteer subjects at each of three infusion rates. Drug analysis was by HPLC and protein binding was determined by ultrafiltration. The disopyramide free fraction was concentration dependent and marked interindividual variability was observed. Disopyramide clearance was independent of time but dependent on total plasma concentration. This can be completely explained by non-linear protein binding since free disopyramide clearance was observed to be independent of free concentration.

Protein Binding of Piretanide in Normal and Uraemic Serum

SummaryThe protein binding of piretanide was assessed by continuous ultrafiltration of sera from six normal subjects and seven uraemic subjects (samples taken immediately pre-dialysis). Throughout the range of piretanide concentrations studied (0.5–4.5 mM), the mean protein binding for uraemic serum was less than that for normal serum. This difference was significant (p<0.05) at piretanide concentrations of 1.5 mM and above, but not at 1 mM where mean protein binding for uraemic serum was 88.1% compared to 94.2% for normal serum. Analysis of piretanide protein binding characteristics using the Rosenthal plot showed no significant differences between uraemic and normal serum with respect to primary or secondary binding sites. Parallel assessment by the Scatchard method suggests, as expected, that albumin is the principal protein moiety responsible for binding piretanide.