Absorption and pharmacokinetics of grapefruit flavanones in beagles

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 glucuromide 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 center dot 24 (0-05-2-08), 0 center dot 021 (0 center dot 001-0 center dot 3) and 0 center dot 09 (0 center dot 034-0 center dot 12) mu mol/l, respectively. The areas under the curves were 23 center dot 161 (14 center dot 04-70 center dot 62) min x mu mol/for nariningin, 1 center dot 78 (0 center dot 09-4 center dot 95) min x mu mol/l for naringenin and 22 center dot 5 (2 center dot 74-99 center dot 23) min x mu mol/l for naringenin glucuronide. The median and range values for mean residence time were 3 center dot 3 (1 center dot 5-9 center dot 3), 2.8 (0 center dot 8-11 center dot 2) and 8 center dot 0 (2 center dot 3-13 center dot 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.