Intestinal absorption of mixed micellar phylloquinone (vitamin K1) is unreliable in infants with conjugated hyperbilirubinaemia: implications for oral prophylaxis of vitamin K deficiency bleeding.
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.


METHODS
Prospective randomised controlled study.


METHODS
Paediatric Liver Unit.


METHODS
Forty four infants less than 6 months of age with conjugated hyperbilirubinaemia.


METHODS
Serum concentrations of vitamin K(1) 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(1) 1 mg intravenously or 2 mg orally. Comparison of K(1) levels 24 hours after oral K(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 low K(1) concentrations, indicative of subclinical vitamin K deficiency. Median serum K(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(1) but to only 1.4 ng/ml after oral administration. In the latter group, the low median value (0.95 ng/ml) and wide range (< 0.15-111 ng/ml) of serum K(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(1) > 10 ng/ml.


CONCLUSIONS
The intestinal absorption of mixed micellar K(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(1) prophylaxis regimens in infants with latent cholestasis.
Pereira
S P
SP
Department of Gastroenterology, The Middlesex Hospital, University College London Hospitals NHS Trust, London, UK. steve.pereira@uclh.org
Shearer
M J
MJ
Williams
R
R
Mieli-Vergani
G
G
D000284:Administration, Oral; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006932:Hyperbilirubinemia / Q000378:metabolism*; D007223:Infant; D007231:Infant, Newborn; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008297:Male; D008823:Micelles; D011446:Prospective Studies; D010837:Vitamin K 1 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014813:Vitamin K Deficiency / Q000150:complications / Q000188:drug therapy; D006475:Vitamin K Deficiency Bleeding / Q000209:etiology / Q000517:prevention & control*
D000933:Antifibrinolytic Agents; D008823:Micelles; D010837:Vitamin K 1