EFFECT OF DIETARY-FAT CONTENT ON ORAL BIOAVAILABILITY OF MENATETRENONE IN HUMANS

The purpose of this investigation was to determine the effects of fat content and frequency of meals on the oral bioavailability of menatetr enone ethyl-3-alf-trans-tetraprenyl-1,4-naphthoquinone), a vitamin K-2 with four isoprene units. in the first series of studies, menatetreno ne (15 mg) was administered at breakfast time to 18 healthy male volun teers after meals with three different fat contents (meals A, B, and C ) on three occasions in a crossover design. The three types of meals h ad almost the same calorie content (721-746 kcal) with varied fat cont ents (A, 8.8 g; B, 20.0 g; C, 34.9 g). The area under the plasma menat etrenone concentration-time curve within the first 24 h (AUC(0-24)) in creased with increase of fat content: 371 +/- 194, 485 +/- 150, and 10 24 +/- 341 ng . h/ml (mean +/- SD, n = 18) after meals A, B, and C, re spectively. On the fourth occasion, the same dose of menatetrenone was administered to all volunteers after taking meal B, but in this case the lunch 5 h after drug administration was omitted from the protocol. The time profile of plasma menatetrenone showed a single peak when lu nch was not taken, whereas it showed two peaks with lunch. On the fift h occasion, 12 out of 18 volunteers took the same dose of menatetrenon e after a meal with the highest fat content (53.8 g of fat and 789 kca l; meal D), showing that AUC(0-24) was almost the same as that for mea l C, 1027 +/- 389 and 991 +/- 392 ng . h/mL (n = 12) for meals C and D , respectively. The oral bioavailability of lipid-soluble vitamin K wa s influenced by the fat content of a meal, although the increase in bi oavailability seemed to reach a peak when the lipid content of the mea l was >35 g.