Absorption and pharmacokinetics of grapefruit flavanones in beagles

Abstract

The present study evaluated the pharmacokinetics of three different grapefruit flavanone forms in dog plasma and demonstrated their absorption after an oral intake of a grapefruit extract; pharmacokinetic parameters of these forms were also determined. Ten healthy beagles were administered 70 mg citrus flavonoids as a grapefruit extract contained in capsules, while two additional dogs were used as controls and given an excipient. The grapefruit flavanone naringin, along with its metabolites naringenin and naringenin glucuronide, was detected in dog plasma. Blood samples were collected between 0 and 24 h after administration of the extract. Naringin reached its maximun plasma concentration at around 80 min, whereas naringenin and naringenin glucuronide reached their maximun plasma concentrations at around 20 and 30 min, respectively. Maximum plasma concentrations of naringin, naringenin and naringenin glucuronide (medians and ranges) were 0·24 (0·05–2·08), 0·021 (0·001–0·3) and 0·09 (0·034–0·12) μmol/l, respectively. The areas under the curves were 23·16 l (14·04–70·62) min × μmol/for nariningin, 1·78 (0·09–4·95) min × μmol/l for naringenin and 22·5 (2·74–99·23) min × μmol/l for naringenin glucuronide. The median and range values for mean residence time were 3·3 (1·5–9·3), 2·8 (0·8–11·2) and 8·0 (2·3–13·1) h for naringin, naringenin and naringenin glucuronide, respectively. The results of the present study demonstrate the absorption of grapefruit flavanones via the presence of their metabolites in plasma, thus making an important contribution to the field since the biological activities ascribed to these compounds rely on their specific forms of absorption.