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Vitamin K1 prophylaxis in neonates is required for prevention of vitamin K1 deficiency bleeding. Although intramuscular administration of vitamin K1 is safe, this invasive method is not generally accepted. We therefore examined the pharmacokinetics of two orally administered vitamin K1 preparations in normal, fully breast-fed newborns.Within 1 hour of birth, each baby was randomized to a 2 mg dose of either a conventional Cremophor EL-solubilized preparation of vitamin K1 (Konakion drops, F. Hoffmann-La Roche, n = 16), or a new mixed-micellar preparation of vitamin K1 (Konakion MM, F. Hoffmann-La Roche, n = 14). The concentrations of vitamin K1, des-γ-carboxyprothrombin (PIVKA-II), and total bound bilirubin were measured in plasma samples taken at 24 hours, 4 days, and 24 days after birth.The median concentration of plasma vitamin K1 was higher at all three time points in the group that received the mixed-micellar preparation, but the difference was only significant (p < 0.05) at 4 days. At 24 hours and 4 days, PIVKA-II was detectable in a significantly lower proportions of infants receiving the new mixed-micellar preparation than those receiving the Cremophor EL preparation (21% vs. 75% at 24 hours, p < 0.05 and 14% vs. 50% at 4 days, p < 0.05). None of the infants in the study had detectable PIVKA-II levels 24 days after birth.Our results suggest that when given orally, the mixed-micellar preparation is superior to the conventional formulation because it increases plasma vitamin K1 concentrations to higher levels, suggesting superior bioavailability, and decreases PIVKA-II concentrations more efficiently, suggesting a faster pharmacodynamic response.