Pharmacokinetics of Luteolin and Metabolites in Rats

Abstract

The pharmacokinetic parameters of luteolin and its glucuronide/sulfate conjugates were studied in rats after a single 50 mg/kg dose of luteolin administered as intravenous bolus or oral solution. Plasma and urine samples were enzymatically hydrolyzed to determine conjugate concentrations of luteolin. Noncompartmental analysis revealed a half-life of 8.94 h for free (unconjugated) and 4.98 h for conjugated luteolin following intravenous administration. Following oral administration, plasma concentrations of luteolin attained a maximum level of 5.5 μg/mL at 5 min and decreased to below LOQ (100 ng/mL) after 1 h. K_e could not be calculated because the elimination phase was below LOQ. The low bioavailability (F) of luteolin, 4.10% at a dose of 50 mg/kg, is presumably due to the significant first pass effect. For i.v. administration, the maximum concentration of luteolin was 23.4 μg/mL at 0 h. The plasma concentration versus time profile of luteolin was biphasic, subdivided into a distribution phase and a slow elimination phase for oral and intravenous administration. Luteolin was found to have a large volume of distribution and a high clearance. Double peaks were found after intravenous and oral administration, suggesting enterohepatic recirculation.