Pharmacokinetics and tolerance of intravenous and intramuscular phylloquinone (vitamin K1) mixed micelles formulation.

1. The pharmacokinetics and tolerance of phylloquinone(vitamin K1) mixed micelles formulation (Konakion MM) were evaluated, in normal human adult volunteers (n = 30) using an open randomized crossover design protocol following a 10 mg intravenous or intramuscular injection. 2. Blood samples were collected for up to 12 h after the intravenous and up to 72 h after the intramuscular injections and the phylloquinone(vitamin K1) levels determined by reversed phase h.p.l.c. with fluorometric detection after post-column electrochemical reduction. 3. Konakion MM was well tolerated after either route of administration. Pharmacokinetic analysis of plasma phylloquinone(vitamin K1) concentration vs time profiles revealed that in one-fifth of the subjects systemic availability of intramuscular phylloquinone (vitamin K1) was below 65%. 4. Our data suggest that due to sustained, but irregular and unpredictable absorption of the phylloquinone(vitamin K1) from the depot site, the intramuscular route of Konakion MM administration is not suitable and thus not recommended. 5. Konakion MM i.v. is indicated to be well tolerated and effective in antagonizing coumarin-type-anticoagulants like Marcoumar.