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

Abstract

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®.