title: Pharmacokinetics, metabolism and excretion of 14C-monoethyl phthalate (MEP) and 14C-diethyl phthalate (DEP) after single oral and IV administration in the juvenile dog.
abstract: The pharmacokinetics, metabolism and excretion of monoethyl phthalate (MEP) and diethyl phthalate (DEP) were compared after intravenous or oral administration of [(14)C]MEP or [(14)C]DEP in juvenile beagle dogs. Four male juvenile beagle dogs were treated with a single oral or bolus intravenous dose of either [(14)C]MEP or [(14)C]DEP (164 μg/kg).        The absorption, metabolism, excretion and pharmacokinetics of [(14)C]MEP and [(14)C]DEP were nearly identical. [(14)C]DEP was rapidly and nearly completely metabolized to [(14)C]MEP following either intravenous or oral administration. [(14)C]MEP and[(14)C]DEP were rapidly absorbed, the elimination half-life was estimated to be 1 hour. Approximately 90%-96% of the dose was excreted in urine with 2%-3% of the dose in faeces. MEP accounted for the majority of the dose in plasma and urine; in addition, three minor metabolites (M1, M2 and M3) were detected. The minor metabolites were neither phthalic acid nor glucuronide/sulfate conjugates.        The nearly identical metabolism and pharmacokinetics of MEP and DEP in juvenile dogs justifies the use of DEP toxicity data in the risk assessment of MEP exposure.
authors: Janssen R&D, Drug Safety Sciences, Raritan, NJ 08869, USA. mkao@its.jnj.com
authors: Mark L
authors: ML
authors: Kao
authors: Bruce
authors: B
authors: Ruoff
authors: Nancy
authors: N
authors: Bower
authors: Toyohiko
authors: T
authors: Aoki
authors: Clair
authors: C
authors: Smart
authors: Geert
authors: G
authors: Mannens
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002250:Carbon Radioisotopes; D004285:Dogs; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D010795:Phthalic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; D010795:Phthalic Acids; C581825:monoethyl phthalate; C007379:diethyl phthalate