PT  - JOURNAL ARTICLE
AU  - B I Ghanayem
AU  - J M Sanders
AU  - A M Clark
AU  - J Bailer
AU  - H B Matthews
TI  - Effects of dose, age, inhibition of metabolism and elimination on the toxicokinetics of 2-butoxyethanol and its metabolites.
DP  - 1990 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 136--143
VI  - 253
IP  - 1
4099  - http://jpet.aspetjournals.org/content/253/1/136.short
4100  - http://jpet.aspetjournals.org/content/253/1/136.full
SO  - J Pharmacol Exp Ther1990 Apr 01; 253
AB  - Acute exposure to 2-butoxyethanol (BE) causes dose- and age-dependent hemolytic anemia in rats. Recently, we have shown that butoxyacetic acid (BAA) is the proximate hemolytic agent and that inhibition of alcohol or aldehyde dehydrogenases protected rats against BE-induced hemolytic anemia. In the present investigations, the kinetics of 14C-BE metabolism and clearance were studied in control adult (3-4 months old) and old (12-13 months old) male F344 rats and in adult male F344 rats treated with pyrazole, cyanamide or probenecid. Our results showed that the area under the curve (AUC), maximum plasma concentration (Cmax) and systemic clearance (Cls) of BE were dose-dependent. In contrast, there was no effect of dose on half-life (T1/2) or volume of distribution (Vd) of BE. These results also showed that there was no age effect on T1/2, Vd or Cls of BE. However, Cmax and AUC of BE increased as a function of age. Also, analysis of variance indicated no significant interactions (P less than or equal to .05) between dose and age in relation to BE kinetics. As expected, inhibition of BE metabolism by pretreatment of rats with pyrazole or cyanamide resulted in a significant increase in the T1/2 and AUC of BE, whereas it caused a significant decrease in the Cls. Furthermore, pyrazole had no effect, whereas cyanamide had decreased Vd of BE. Analysis of the toxicokinetic parameters of BAA revealed that T1/2, AUC and Cmax of BAA were directly related to the age of the rats and the dose of BE administered.(ABSTRACT TRUNCATED AT 250 WORDS)