Cyclic interconversion of vitamin K1 and vitamin K1 2,3‐epoxide in man.

Abstract

The disposition of a single intravenous bolus dose of 10 mg vitamin K1 and vitamin K1‐2,3‐epoxide were studied in two healthy subjects without and with 12 h pretreatment dose of phenprocoumon (0.4 mg/kg). For each compound administered alone the plasma concentration‐time profile was adequately fitted by a biexponential equation, with an average terminal half‐life of 2.0 and 1.15 h for the administered vitamin K and its 2,3‐ epoxide respectively. While vitamin K1 was measurable in plasma following administration of vitamin K1‐2,3‐epoxide, the epoxide was not detectable following administration of vitamin K1. Following pretreatment with phenprocoumon and after intravenous administration of vitamin K1, both the average half‐life and area under the plasma concentration‐time profile of vitamin K1 were marginally reduced to 1.5 h and 1.76 mg l‐1 h respectively, while the plasma concentration of vitamin K1‐2,3‐epoxide was readily measurable and its half‐life markedly prolonged to 14.7 h. Following pretreatment with phenprocoumon and after oral administration of vitamin K1‐2,3‐epoxide, no vitamin K1 was detectable in plasma and the half‐life of the epoxide was 13.8 h. Based on area considerations the data suggest that either phenprocoumon does more than just inhibit the reduction of vitamin K1‐2,3‐epoxide to vitamin K1, or that the simple model describing the interconversion between vitamin K1 and its epoxide is inadequate. The same conclusion is drawn from the analysis of comparable data in dogs, obtained by Carlisle & Blaschke (1981).

Congenital Deficiency of All Vitamin K-Dependent Blood Coagulation Factors Due to a Defective Vitamin K-Dependent Carboxylase in Devon Rex Cats

“…In normal mammalian liver any KO formed is readily reduced by the enzyme KO-reductase, and no KO is detectable in blood plasma. It is well known, however, that in the case of a decreased KO-reductase activity substantial amounts of KO are set free in the blood stream, especially after the administration of high doses of vitamin K (20). No elevated KO concentrations were found, however (data not shown).…”

Plasma disposition of vitamin K1 in relation to anticoagulant poisoning.

“…0.3 mg; Bjornsson et al, 1979). Thus there is no evidence for pronounced dosedependency in the pharmacokinetics of the vitamin (Bechtold et al, 1983). Coumarin anticoagulants do not alter the plasma disposition of vitamin K, in either man (Shearer et al, 1977) or the rabbit (Park et al, 1980).…”

A Comprehensive Model for the Humoral Coagulation Network in Humans

“…where p VKDF is the production rate of vitamin K–dependent coagulation factor or protein, assumed to be proportional to the concentration of VKH 2 . The half‐life of vitamin K seems to be short in reality, 21 , 38 and yet the literature describes vitamin K as having a long half‐life 39 . This apparent discrepancy is explained by the fact that vitamin K displays two‐compartment pharmacokinetics, with a deeper compartment having a second half‐life; one compartment represents turnover in the vascular and related compartments (relatively short), and the other represents a deeper compartment of tissues and thus a longer half‐life relative to the vascular compartment.…”