additionally I have found a paper by Yvonne van Leeuwen which contains some interesting pieces:
Worldwide there are different types of vitamin K antagonists available. The vitamin K antagonists most frequently used are warfarin, acenocoumarol and phenprocoumon. Warfarin is the vitamin K antagonist of choice in the United States of America, the United Kingdom and many other countries around the world; acenocoumarol and phenprocoumon are frequently used in many European countries. These three vitamin K antagonists mainly differ in their half-life. Acenocoumarol has the shortest half-life of 11 hours, followed by warfarin with 36-42 hours and the longest half-life is seen in phenprocoumon with approximately 140 hours. The clearance of these vitamin K antagonists is also different. Acenocoumarol is for its elimination completely dependent on hydroxylation by cytochrome p450 (CYP). Warfarin is also dependent on reduction processes [12]. Phenprocoumon can, in addition to elimination as hydroxylated metabolites, be eliminated as parent compound and is thus less dependent on hydroxylation by CYP.
this last piece refers to how the body 'clears' the compound from itself. the Cytochrome pathway is important to removal of 'toxins' from the body ... oh and as far as I know its based on our cells mitochondria.
Next something for protimenow:
Although the PT is sensitive for anticoagulation with vitamin K antagonists, the tests are poorly standardised between different laboratories. Use of different reagents and equipment results in substantially different PT values from a single blood sample.
The risk for complications rises sharply with INR values below 2.0 and exponentially with INR values above 5.0
She notes (of clinic testing I assume) that
Approximately 30 to 50% of the time, patients’ INR is out of range
this figure is much improved by self testing in all the papers I have ever read.
She also studies computer based algorithms (far more complex than I have created in my simple model) and compared two (ICAD and TRODIS)
with respect to doses in 'transition' between various coumarin drugs. I find it interesting that she makes the point that they are part of the same family group, and so perhaps there is little difference. On why people may switch she observes:
sensitivity can be a reason to switch from one coumarin to the other for practical reasons,since a maintenance dose of less than 1 mg of acenocoumarol is difficult to administer (tablets contain 1 mg, and cannot be divided).
in a note about the literature she says:
At present, literature about the transition from one coumarin to another is surprisingly scarce. One study investigated a dosage scheme for transition from phenprocoumon to warfarin in patients treated in an outpatients clinic [20]. The authors found that the dosage for an optimal INR of warfarin is 2.3 times the dosage of phenprocoumon.
so the actual dosage in mg may be different between phenprocoumon and warfarin.
She later observes:
The transition factor between the maintenance dosage of phenprocoumon and warfarin in milligram was 0.41 (95% CI 0.39 – 0.43), indicating that the maintenance dosage of phenprocoumon is 0.41 times the maintenance dosage of warfarin (figure 2).
which supports that.
What effect this has I can't say. Just because you take more or less of it is not specifically a reason to be concerned about other effects. Clearly "more research is needed" to answer that question.
At the very least the usage of Warfarin (being a larger dose) will make it
easier to 'tune' your dose as a change from (say) 7mg daily to 7.5mg daily would be easier than 2.87mg of phenprecoumin to 3.075mg
I think that a significant thing emerges from all my readings (to date) on INR and various coumarins is this:
the cohort studied is older, with a median age of late 60s in most studies. I would expect that this biases the observations as to health effects because (hopefully) people in their 60's are not as healthy as people in their mid 30's...
I have the paper (150 pages) if anyone wants a copy PM me with an email address.
