Pharmacokinetics of methyl parathion: a comparison following single intravenous, oral or dermal administration.
Assessment of the risks posed by the residential use of methyl parathion requires an understanding of its pharmacokinetics after different routes of exposure. Thus, studies were performed using adult female rats to define the pharmacokinetic parameters for methyl parathion after intravenous injection and to apply the described model to an examination of its pharmacokinetics after single oral or dermal exposure. The pharmacokinetics of methyl parathion after intravenous administration (1.5 mg/kg) were best described by a three-compartment model; the apparent volume of the central compartment was 1.45 liters/kg, clearance was 1.85 liters/h/kg and the terminal half-life was 6.6 h with an elimination constant of 0.50 h(-1). The apparent oral absorption coefficient for methyl parathion (1.5 mg/kg) was 1.24 h(-1), and its oral bioavailability was approximately 20%. The latter likely includes a significant first pass effect. Concentrations of methyl parathion increased during the initial 10-60 min and then declined during the next 15-36 h. After dermal administration (6.25-25 mg/kg), methyl parathion concentrations peaked within 12-26 h and then declined dose dependently. The apparent dermal absorption coefficient was approximately 0.41 h(-1), and only two pharmacokinetic compartments could be distinguished. In conclusion, the pharmacokinetics of methyl parathion are complex and route dependent. Also, dermal exposure, because of sustained methyl parathion concentrations, may pose the greatest risk.
Kramer
Robert E
RE
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA. rkramer@pharmacology.umsmed.edu
Wellman
Susan E
SE
Rockhold
Robin W
RW
Baker
Rodney C
RC
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D007275:Injections, Intravenous; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008433:Mathematics; D008743:Methyl Parathion / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D008743:Methyl Parathion