Menaquinone-4 Accumulation in Various Tissues After an Oral Administration of Phylloquinone in Wistar Rats

The distributions of phylloquinone (PK) and menaquinone-4 (MK-4) in various tissues were assessed after the oral administration of phylloquinone. Wistar rats were fed a vitamin-K-deficient diet for nine days, fasted for 24 h and then given phylloquinone orally at 4 mg/kg body weight. Rats were sacrificed 0, 6, 12 and 24 h after the administration, and an analysis was made of the vitamin K analogues in the plasma, liver, brain, testis, kidney and spleen. The phylloquinone concentration in plasma and the tissues reached a peak 6 h after the oral administration of phylloquinone. By contrast, the concentration of MK-4 peaked in the liver, plasma, kidney and spleen at 12 h, and in brain and testis at 24 h. This data suggests that the ingested phylloquinone was probably converted into MK-4 within the tissues themselves, rather than via hepatic metabolism. The evidence for this is that, after phylloquinone administration, (i) in each of the tissues, the MK-4 concentration increased much more slowly than that of phylloquinone, and (ii) the MK-4 concentration in the plasma and liver reached only much lower levels than those seen in other tissues.