title: Intestinal absorption of mixed micellar phylloquinone (vitamin K1) is unreliable in infants with conjugated hyperbilirubinaemia: implications for oral prophylaxis of vitamin K deficiency bleeding.
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.
  
  
  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.
authors.affiliation: Department of Gastroenterology, The Middlesex Hospital, University College London Hospitals NHS Trust, London, UK. steve.pereira@uclh.org
authors.forename: S P
authors.initials: SP
authors.lastname: Pereira
authors.forename: M J
authors.initials: MJ
authors.lastname: Shearer
authors.forename: R
authors.initials: R
authors.lastname: Williams
authors.forename: G
authors.initials: G
authors.lastname: Mieli-Vergani
mesh_terms: 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*
chemical_list: D000933:Antifibrinolytic Agents; D008823:Micelles; D010837:Vitamin K 1