Effect of dosing vehicles on the pharmacokinetics of orally administered carbon tetrachloride in rats

摘要: The primary objectives of this investigation were to determine whether oil and aqueous dosage vehicles alter the pharmacokinetics orally administered carbon tetrachloride (CCl4) in rats, relate vehicle effects on CCl4 absorption bioavailability alterations acute hepatotoxicity seen a companion study (H.J. Kim, S. Odend'hal, J. V. Bruckner, 1990, Toxicol. Appl. Pharmacol. 102, 34-49). Fasted 200- 230-g male Sprague-Dawley rats with indwelling arterial cannulas received 25 mg CCl4/kg body wt by gavage: corn oil; as an Emulphor emulsion; water; pure undiluted chemical. mg/kg dose was also given iv PEG 400 through jugular cannula. Serial blood samples taken from gavage animals analyzed for content obtain concentration-versus-time profiles. absorbed very rapidly GI tract, peak concentrations reached within 3-6 min dosing emulsion water groups. These levels higher than those group substantially group. Corn markedly delayed tract produced secondary peaks Elimination bloodstream followed triexponential pattern. eliminated at approximately same rate po groups, reflected similar elimination constant half-life values. There high degree correlation both Cmax AUC0(120) hepatotoxicity. apparently less acutely hepatotoxic due delay prolongation absorption, resulting marked decrease concentration chemical blood. findings suggest that has sufficient effect require appraisal its use studies oral toxicity other volatile organic chemicals (VOCs). emulsions appears appropriate VOC contaminants drinking water, did not or ingested water.