Pharmacokinetic study of p-chloronitrobenzene in humans suffering from acute poisoning.
The pharmacokinetics of p-chloronitrobenzene (p-CNB) in human subjects suffering from acute poisoning was studied from the urinary excretion of p-CNB metabolites. The time course for excretion of five metabolites--2-chloro-5-nitrophenol,N-acetyl-S-(4-nitrophenyl)- L-cysteine, 2,4-dichloroaniline, p-chloroaniline, and 2-amino-5-chlorophenol-were determined by reversed-phase HPLC analysis of urine collected from six subjects during their hospitalization after accidental exposure to p-CNB. The cumulative excretion amount at infinite time (X infinity) and mean residence time for each metabolite were estimated by moment analysis of excretion rate vs. the time curve. The rate constants for p-CNB metabolism were calculated by nonlinear least squares fitting of the time course data using a one-compartment model. The results indicated that the average values of the ratio of excreted amount of each metabolite to the total amount of the five metabolites (X infinity metabolite/X infinity Total) and mean residence time in the six subjects were, respectively: 12.2% and 6.7 days for 2-chloro-5-nitrophenol, 48.0% and 7.0 days for N-acetyl-S-(4-nitrophenyl)-L-cysteine, 1.2% and 3.7 days for 2,4-dichloroaniline, 29.9% and 10.0 days for p-chloroaniline, and 8.7% and 6.0 days for 2-amino-5-chlorophenol. The average values of rate constants in the metabolism of p-CNB to 2-chloro-5-nitrophenol, N-acetyl-S-(4-nitrophenyl)-L-cysteine, and p-chloroaniline were 0.021, 0.082, and 0.067 day-1, respectively. Similarly those in further metabolism of p-chloroaniline for C-chlorination, C-hydroxylation, and N-conjugation were 0.205, 1.206, and 3.526 day-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Yoshida
T
T
Osaka Prefectural Institute of Public Health, Japan.
Tabuchi
T
T
Andoh
K
K
D000208:Acute Disease; D000328:Adult; D001711:Biotransformation; D001825:Body Fluid Compartments; D003404:Creatinine / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009578:Nitrobenzenes / Q000493:pharmacokinetics* / Q000506:poisoning* / Q000652:urine; D011041:Poisoning / Q000378:metabolism / Q000652:urine
D009578:Nitrobenzenes; D003404:Creatinine; C010407:4-chloronitrobenzene