Plasma profiles of lycopene after single oral and intravenous administrations in dogs

Abstract

The objectives of this study were to identify the factors limiting the absorption of purified lycopene after oral administration, and to comparatively assess plasma data sets after single oral and intravenous administrations in dogs to define the conditions for performing an absolute bioavailability study. Solubility of purified lycopene (all-trans, 93.5%) was determined in media simulating the conditions in the fasted and in the fed upper gastrointestinal lumen. After evaluating the plasma levels achieved following single administrations of purified lycopene powder to fasted and fed dogs at escalating doses (75-750 mg), a crossover study was performed in four fed female mongrel dogs at two phases. In phase I, one soft gelatine capsule (10 mg lycopene) with 500 mL milk was administered orally. In phase II, 500 mL milk was administered orally and 250 mL 5% dextrose containing 5 mg lycopene in the form of a binary system with hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) was administered intravenously over 3.5 h. In-vitro and preliminary canine studies confirmed that, after oral administration of lycopene in solid form, arrival of lycopene into the systemic circulation was limited by lymphatic transport and, in addition, if the administered dose was higher than approximately 2 mg, by intralumenal solubility. During the first 50 h after single administrations to fed dogs, lycopene plasma levels were lower after intravenous than after oral administration. This could have been related to capacity limited elimination of lycopene and/or route-dependent disposition kinetics. Estimation of the amount of lycopene reaching the systemic circulation after oral and after intravenous administration requires separate estimations of total body clearance of lycopene.