Application of molecular encapsulation for toxicology studies: toxicokinetics of p-chloro-alpha,alpha,alpha-trifluorotoluene in alpha-cyclodextrin or corn oil vehicles in male F344 rats.
Toxicokinetics of p-chloro-alpha,alpha,alpha-trifluorotoluene (CTFT) after administration as an aqueous alpha-cyclodextrin (alpha-CD) molecular encapsulation suspension (alpha-CD vehicle) or as a corn oil solution (corn oil vehicle) were compared. Male F344 rats were administered intragastrically CTFT in alpha-CD vehicle or corn oil vehicle at dose levels of 10, 50, or 400 mg/kg. Other male F344 rats were administered CTFT intravenously in a 10% Tween 80 aqueous solution. Serial blood samples were taken from a cannulated jugular vein for up to 52 hr after dosing and the CTFT concentrations in whole blood were determined by gas chromatography. The biological elimination half-life of CTFT from the center compartment was not affected by the vehicle used; however, absorption of CTFT from the alpha-CD vehicle was much faster than from the corn oil vehicle. The average absorption half-lives from the alpha-CD vehicle and corn oil vehicle were 17 and 98 min, respectively. Despite the differences in absorption, no statistical difference was observed in the calculated areas under the blood concentration versus time curves (AUC) obtained from rats dosed with either vehicle. Dose proportionality for CTFT was established up to 400 mg/kg and bioavailability was shown to be complete for both vehicles.
Yuan
J M
JM
National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Jameson
C W
CW
Goehl
T J
TJ
Collins
B J
BJ
Purdie
W
W
Judd
L
L
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003314:Corn Oil / Q000008:administration & dosage*; D003505:Cyclodextrins / Q000008:administration & dosage*; D004339:Drug Compounding; D007275:Injections, Intravenous; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D014050:Toluene / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D011136:Polysorbates; D047391:alpha-Cyclodextrins; D014050:Toluene; C037723:4-chloro-alpha,alpha,alpha-trifluorotoluene; D003314:Corn Oil; C032613:alpha-cyclodextrin