TITLE

Intestinal absorption of mixed micellar phylloquinone (vitamin K[sub 1]) is unreliable in infants with conjugated hyperbilirubinaemia: Implications for oral prophylaxis of vitamin K deficiency bleeding

AUTHOR(S)
Pereira, S.P.; Shearer, M.J.; Williams, R.; Mieli-Vergani, G.
PUB. DATE
March 2003
SOURCE
Archives of Disease in Childhood -- Fetal & Neonatal Edition;Mar2003, Vol. 88 Issue 2, pF113
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Objective: To compare the pharmacokinetics and efficacy of oral versus intravenous mixed micellar vitamin K prophylaxis in infants with cholestatic liver disease, a known risk factor for vitamin K deficiency bleeding. Design: Prospective randomised controlled study. Setting: Paediatric Liver Unit. Patients: Forty four infants less than 6 months of age with conjugated hyperbilirubinaemia. Main outcome measures: Serum concentrations of vitamin K, and undercarboxylated prothrombin (PIVKA-II; a sensitive functional indicator of vitamin K status) before and for up to four days after a single dose of mixed micellar K[sub 1] 1 mg intravenously or 2 mg orally. Comparison of K[sub 1] levels 24 hours after oral K[sub 1] with those from 14 healthy newborns given the same dose. Results: At admission, 18 infants (41%) had elevated levels of serum PIVKA-II and eight (18%) had Iow K, concentrations, indicative of subclinical vitamin K deficiency. Median serum K[sub 1] concentrations were similar in the oral and intravenous groups at baseline (0.92 v 1.15 ng/ml), rising to 139 ng/ml six hours after intravenous K[sub 1] but to only 1.4 ng/ml after oral administration. In the latter group, the Iow median value (0.95 ng/ml) and wide range (< 0.15-111 ng/ml) of serum K[sub 1] compared unfavourably with the much higher levels (median 77, range 11-263 ng/ml) observed in healthy infants given the same oral dose, and suggested impaired and erratic intestinal absorption in cholestatic infants. The severity of malabsorption was such that only 4/24 (17%) achieved an incremental rise in serum K[sub 1] > 10 ng/ml. Conclusions: The intestinal absorption of mixed micellar K[sub 1] is unreliable in infants with conjugated hyperbilirubinaemia. 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[sub 1] prophylaxis regimens in infants with latent cholestasis.
ACCESSION #
9723638

 

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