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Drug Metabolism and Disposition Fast Forward
First published on October 4, 2004; DOI: 10.1124/dmd.104.000893

0090-9556/05/3301-49-54$20.00
DMD 33:49-54, 2005

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PHARMACOKINETICS AND METABOLISM OF APIGENIN IN FEMALE AND MALE RATS AFTER A SINGLE ORAL ADMINISTRATION

Angéline Gradolatto, Jean-Philippe Basly, Raymond Berges, Caroline Teyssier, Marie-Christine Chagnon, Marie-Héléne Siess, and Marie-Chantal Canivenc-Lavier

Unité Mixte de Recherche de Toxicologie Alimentaire, Institut National de la Recherche Agronomique, Dijon cedex, France (A.G., R.B., C.T., M-.C.C., M.-H.S., M.-C.C.-L.); and Laboratoire de Chimie Analytique et Bromatologie, Unité de Formation et de Recherche de Pharmacie, Limoges, France (J.-P.B).

The metabolism of apigenin, a weak estrogenic flavonoid phytochemical, was investigated in the rat. After a single oral administration of radiolabeled apigenin, 51.0% of radioactivity was recovered in urine, 12.0% in feces, 1.2% in the blood, 0.4% in the kidneys, 9.4% in the intestine, 1.2% in the liver, and 24.8% in the rest of the body within 10 days. Sex differences appear with regard to the nature of compounds eliminated via the urinary route: immature male and female rats, like mature female rats, excreted a higher percentage of the mono-glucuronoconjugate of apigenin than the mono-sulfoconjugate of apigenin (10.0-31.6% versus 2.0-3.6%, respectively). Mature male rats excreted the same compounds in an inverse ratio (4.9% and 13.9%, respectively). Radioactivity appeared in the blood only 24 h after oral administration. Blood kinetics showed a high elimination half-time (91.8 h), a distribution volume of 259 ml, and a plasmatic clearance of 1.95 ml/h. All of the parameters calculated from these experiments suggested a slow metabolism of apigenin, with a slow absorption and a slow elimination phase. Thus, a possible accumulation of this flavonoid in the body can be hypothesized.

Address correspondence to: Marie-Chantal Canivenc-Lavier, Unité Mixte de Recherche de Toxicologie Alimentaire, INRA, 17 rue Sully, BP 86510, 21065 Dijon cedex, France. E-mail: canivenc{at}dijon.inra.fr




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