P M Loughnan1, P N McDougall. 1. Department of Neonatology, Royal Children's Hospital, Parkville, Victoria, Australia.
Abstract
OBJECTIVE: To propose a hypothesis that the long duration of effect of intramuscular (i.m.) vitamin K1 in preventing late onset haemorrhagic disease results from a depot effect after i.m. injection. METHODOLOGY: Review of scientific literature relating to the pharmacology of vitamin K, and the aetiology of late onset haemorrhagic disease. RESULTS: A single i.m. dose of vitamin K1 is effective for at least 2 months, whereas the duration of effect of a single oral dose is about 3-4 weeks. The known pharmacological properties of vitamin K1 are seemingly at variance with the long duration of effect of an i.m. dose. Menaquinones (vitamins K2) are absent in the newborn liver, but gradually accumulate after birth. This, together with the low concentrations of vitamin K1 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 K1 acts as a depot preparation by forming a viscous mass in muscle tissue which is slowly absorbed over many weeks. This hypothesis is supported by reports indicating significantly higher plasma vitamin K1 levels several weeks after i.m., as compared to oral vitamin K1. CONCLUSIONS: The prolonged efficacy of i.m. vitamin K1, compared to oral preparations may be due to a depot effect. New oral preparations of vitamin K1, despite greatly improved bioavailability, may have a shorter duration of effect than i.m. vitamin K1, and therefore be less effective for long-term prophylaxis.
OBJECTIVE: To propose a hypothesis that the long duration of effect of intramuscular (i.m.) vitamin K1 in preventing late onset haemorrhagic disease results from a depot effect after i.m. injection. METHODOLOGY: Review of scientific literature relating to the pharmacology of vitamin K, and the aetiology of late onset haemorrhagic disease. RESULTS: A single i.m. dose of vitamin K1 is effective for at least 2 months, whereas the duration of effect of a single oral dose is about 3-4 weeks. The known pharmacological properties of vitamin K1 are seemingly at variance with the long duration of effect of an i.m. dose. Menaquinones (vitamins K2) are absent in the newborn liver, but gradually accumulate after birth. This, together with the low concentrations of vitamin K1 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 K1 acts as a depot preparation by forming a viscous mass in muscle tissue which is slowly absorbed over many weeks. This hypothesis is supported by reports indicating significantly higher plasma vitamin K1 levels several weeks after i.m., as compared to oral vitamin K1. CONCLUSIONS: The prolonged efficacy of i.m. vitamin K1, compared to oral preparations may be due to a depot effect. New oral preparations of vitamin K1, despite greatly improved bioavailability, may have a shorter duration of effect than i.m. vitamin K1, and therefore be less effective for long-term prophylaxis.