The antiepileptic drugs, phenobarbital and phenytoin, were determined in plasma by enzyme immunoassay (EMIT) and by high-pressure liquid chromatography (HPLC). In addition, the major metabolite of phenytoin, p-hydroxydiphenylhydantoin (HPPH), was determined by HPLC. Within-day and between-day coefficients of variation for both methods were 7.6% or less for phenobarbital and 8.7% or less for phenytoin, and for HPPH, by liquid chromatography, were 7.4% or less. Both methods also showed good linearity from subtherapeutic through low toxic concentrations. Comparison of the results of the two methods for phenobarbital and for phenytoin showed good correlations r = 0.99 and 0.97 respectively, indicating that HPLC can be used rather than the more commonly used EMIT. In addition, this HPLC method simultaneously measures both antiepileptic drugs and the unconjugated form of the major metabolite of phenytoin, and with prior hydrolysis, the conjugated form of p-hydroxydiphenylhydantoin.

Biotransformation↗

PubMedDate not supplied

Toxicity of chlorine dioxide in drinking water.

Chlorine dioxide (ClO2) is currently being considered as an alternate to chlorine as a disinfectant for public water supplies. Studies were conducted to determine the toxicity of ClO2 (0, 1, 10, 100, 1000 mg/l) and its metabolites, ClO3- and ClO3- (10, 100 mg/l) in drinking water in rats. After nine months treatment the osmotic fragility of the red blood cells was decreased in all treatment groups, while a decreased blood glutathione was only observed in the metabolite groups. At 2, 4 and 6 mon no significant hematologic changes were noted in treated rats compared to control. However, after 9 mon RBC counts, hematocrit and hemoglobin were decreased in all treatment groups. ClO2, ClO2- and ClO3- administered chronically in drinking water for three months inhibited the incorporation of 3H-thymidine into nuclei of rat testes. Also, this inhibition was observed in the liver of ClO2- groups and in the kidney of 100 mg/l ClO2- treatment. The incorporation in small intestinal nuclei was increased in both 10 and 100 mg/l ClO2 and in 10 mg/l ClO2-. The treatment with Cl-compounds decreased rat body weight in all groups after 10 and 11 months treatment.

Animals↗

PubMedDate not supplied

The kinetics of chlorite and chlorate in rats.

Chlorine dioxide (ClO2) is under consideration as an alternative to chlorination as a disinfectant for public water supplies. The primary products resulting from ClO2 disinfection of surface waters are chlorite (ClO2-) and chlorates (ClO3-). The kinetics of 36ClO2- and 36ClO3- was studied in rats. Radioactivity was rapidly absorbed from the gastrointestinal tract following the administration of (0.17 microCi) 36ClO2- or (0.85 microCi) 36ClO3- orally; and 36Cl in plasma reached a peak at 2 hr and 1 hr, respectively. After 72 hr, radioactivity was highest in whole blood, followed by packed cells, plasma, stomach, testes, skin, lung, kidney, duodenum, carcass, spleen, ileum, brain, bone marrow and liver in 36ClO2- treatment. 36Cl excretion was greatest at 24 hr after the administration of 36ClO3-, but in the 36ClO2-, the excretion most likely represented saturation of the biotransformation and excretion pathways. About 40% of the total initial dose was excreted at 72 hr in the urine and feces in both treatments. No 36Cl was detected in expired air throughout the 72 hr studied.

Animals↗