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Vitamin K(1) Absorption Unreliable in Infants with Conjugated Hyperbilirubinaemia

Intestinal absorption of mixed micellar phylloquinone (vitamin K[1]) is unreliable in infants with conjugated hyperbilirubinaemia and may be the reason some oral prophylaxis regimens fail to work in these children.

Only 17% of cholestatic infants achieve an incremental rise in serum K(1) greater than 10 ng/mL with oral administration, report investigators led by Dr. Steven Pereira of Middlesex Hospital at University College London Hospital National Health Trust in London, England.

"Given the strong association between cholestasis and late vitamin K deficiency bleeding, these data provide an explanation for the failure of some oral vitamin K(1) prophylaxis regimens in infants with latent cholestasis," they concluded.

The pharmacokinetics and efficacy of oral versus intravenous (IV) mixed micellar vitamin K prophylaxis was evaluated in 44 children younger than 6 months who were diagnosed with conjugated hyperbilirubinaemia. Results of oral administration at 24 hours were also compared with those of 14 healthy newborns given the same oral dose. The IV dose was 1 mg, while the oral dose was 2 mg.

Before and up to 4 days after a single dose of mixed micellar K(1), the researchers evaluated serum concentrations of vitamin K(1) and under-carboxylated prothrombin (PIVKA-II), a sensitive indicator of vitamin K status.

At baseline, 41% of infants had elevated serum PIVKA-II levels; 18% had low K(1) concentrations, which indicated sub-clinical vitamin K deficiency. Median serum K(1) concentrations in both the IV and oral groups were similar at baseline.

Median serum K(1) concentrations rose to 139 ng/mL 6 hours after IV K(1), but to only 1.4 ng/mL after oral administration.

Concentrations in infants who received the oral formulation compared unfavourably with much higher levels in healthy children given the same oral dose, the investigators point out. They say this suggests impaired and erratic intestinal absorption in cholestatic infants.
Arch Dis Child Fetal Neonatal Ed 2003 Mar;88:2:F113-F118. "Intestinal absorption of mixed micellar phylloquinone (vitamin K(1)) is unreliable in infants with conjugated hyperbilirubinaemia: implications for oral prophylaxis of vitamin K deficiency bleeding."

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