Pharmacokinetics of caffeic acid phenethyl ester and its catechol‐ring fluorinated derivative following intravenous administration to rats

Abstract

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.

Caffeic acid phenethyl ester induced cell cycle arrest and growth inhibition in androgen-independent prostate cancer cells via regulation of Skp2, p53, p21Cip1 and p27Kip1

“…The achievable physiological concentration of CAPE in human serum is 17 μM [27], therefore, administration of CAPE is a possible treatment for CRPC. CAPE is distributed extensively into animal tissues and is eliminated rapidly with a short half life [28]. Toxicology study revealed that i.p.…”

Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review)

“…CAPE inhibits cytokine and chemokine production, the proliferation of T cells and lymphokine production, and thus suppresses the inflammatory process. Specifically, CAPE is a potent and a specific inhibitor of nuclear factor-κB (NF-κB) activation, and this may provide the molecular basis for its multiple anti-inflammatory and immunomodulatory activities (2,7). The aim of this review is to highlight the anti-inflammatory and immunomodulatory activities of CAPE, focusing on the mechanisms of action (already identified) underlying this activity.…”

Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

“…In addition to the pharmacodynamic point of view, the ester group in CAPE structure is metabolically very labile and limited for their use. Moreover, the phenoxy moieties of CA are fully ionized in alkali intestinal fluid and consequently reduce the absorption from intestine to blood circulation (Crozier et al, 2009;Wang et al, 2009;Gao and Hu, 2010). In the present study, the discovery of lead compound, CIU1 was achieved by structural modification of CA which was composed of (i) extension of molecular structure via urea linker to enhance drug-target interactions, (ii) side chain optimization using selected motif, and (iii) esterification of phenoxy groups to prevent ionization (Fig.…”