Pharmacokinetics of caffeic acid phenethyl ester and its catechol-ring fluorinated derivative following intravenous administration to rats.
The pharmacokinetic profiles of caffeic acid phenethyl ester (CAPE) and its catechol-ring fluorinated derivative (FCAPE) were determined in rats after intravenous administration of 5, 10 or 20 mg/kg for CAPE and 20 mg/kg for FCAPE, respectively. The plasma concentrations of CAPE and FCAPE were measured using a validated liquid chromatography tandem mass spectrometric method. The pharmacokinetic parameters were estimated using non compartmental analysis (NCA) and biexponential fit. The results showed that the area under the plasma concentration-time curve for CAPE treatment increased in a proportion greater than the increase in dose from 5 to 20 mg/kg of CAPE. Total body clearance values for CAPE ranged from 42.1 to 172 ml/min/kg (NCA) and decreased with the increasing dose of CAPE. Similarly, the volume of distribution values for CAPE ranged from 1555 to 5209 ml/kg, decreasing with increasing dose. The elimination half-life for CAPE ranged from 21.2 to 26.7 min and was independent of dose. That FCAPE was distributed extensively into rat tissues and eliminated rapidly was indicated by a high value of volume of distribution and similar short elimination half-life as that of CAPE.
Wang
Xinyu
X
Pharmaceutics Division, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, USA.
Pang
Jihai
J
Maffucci
Jacqueline A
JA
Pade
Devendra S
DS
Newman
Robert A
RA
Kerwin
Sean M
SM
Bowman
Phillip D
PD
Stavchansky
Salomon
S
D000818:Animals; D019540:Area Under Curve; D002109:Caffeic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D017711:Nonlinear Dynamics; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D002109:Caffeic Acids; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol