Interactions of carbon tetrachloride and promethazine in the rat—I: Effects of promethazine on the concentrations of carbon tetrachloride in blood and liver, and on the production of chloroform

The effects of Promethazine (PM, 78 μmoles/kg body wt, i.p.) on the concentrations of CCl 4 in samples of blood and liver of male, fasted rats after oral dosing with CCl 4 have been determined. With an administered dose of CCl 4 of 13 moles/kg body wt the concentrations of CCl 4 in the blood and liver were measured using gas chromatography with a flame ionisation detector. It was found that Promethazine delayed absorption of CCl 4 from the gastro-intestinal tract by approximately 2 hr as judged by blood levels of CCl 4; the maximum blood concentration ( C max) and the total absorption of ccl 4 (assessed by the area under the plot of blood concentration vs time during the first 6 hr after administration of CCl 4) were not significantly changed by Promethazine treatment. Liver and blood measurements were carried out on each rat in this series and the ratio of the CCl 4-concentrations in liver: blood were found to lie within the range 8–12 when studied in the absence of Promethazine treatment. Gas chromatography with electron capture was used on serial samples of blood from the same rat to measure CCl 4 and CHCl 3 concentrations following oral administration of 13, 6.5 or 1.3 mmoles CCl 4/kg body wt. The increase in blood CCl 4 levels at all doses of CCl 4 administered was delayed by about 2 hr by administration of Promethazine. The maximum blood concentrations of CCl 4 and total amount absorbed (judged by area under the plot of blood concentration vs time) were dose-related to the amount of CCl 4 administered with or without Promethazine administration. Blood concentrations of CHCl 3 were relatively constant over the range of CCl 4-doses used indicating that the metabolic production rate of CHCl 3 is saturated at rather low doses of CCl 4 administered.