DOES INTRAMUSCULAR VITAMIN-K-1 ACT AS AN UNINTENDED DEPOT PREPARATION

Objective: To propose a hypothesis that the long duration of effect of intramuscular (i.m.) vitamin K-1 in preventing late onset haemorrhagi c disease results from a depot effect after i.m. injection. Methodolog y: Review of scientific literature relating to the pharmacology of vit amin K-1 and the aetiology of late onset haemorrhagic disease. Results : A single i.m. dose of vitamin K-1 is effective for at least 2 months , whereas the duration of effect of a single oral dose is about 3-4 we eks. The known pharmacological properties of vitamin K-1 are seemingly at variance with the long duration of effect of an i.m. dose. Menaqui nones (vitamins K-2) are absent in the newborn liver, but gradually ac cumulate after birth. This, together with the low concentrations of vi tamin K-1 in human breast milk, may explain the peak frequency of late onset haemorrhagic disease at 4-8 weeks. We hypothesize that after i. m. injection, vitamin K-1 acts as a depot preparation by forming a vis cous mass in muscle tissue which is slowly absorbed over many weeks. T his hypothesis is supported by reports indicating significantly higher plasma vitamin K-1 levels several weeks after i.m., as compared to or al vitamin K-1. Conclusions: The prolonged efficacy of i.m. vitamin K- 1, compared to oral preparations may be due to a depot effect New oral preparations of vitamin K-1, despite greatly improved bioavailability , may have a shorter duration of effect than i.m. vitamin K-1, and the refore be less effective for long-term prophylaxis.