Warfarin metabolism and vitamin K requirement in the warfarin-resistant rat

Hermodson, MA; Suttie, J. W.; Link, K. P.

doi:10.1152/ajplegacy.1969.217.5.1316

Cited by 94 publications

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“…The diets are described in Table 1 (Greenstein et al 1957;Winitz et al 1965) The control diet contained 75 (SD 5) mg phylloquinone as listed in food tables (Booth et al 1996a;Shearer et al 1996) and the low-vitamin K diet contained 8 (SD 2) mg phylloquinone as listed in the above food tables and determined by a bioassay in warfarin-resistant rats (Hermondson et al 1969). Samples of blood, urine and faeces were collected for 6 d after each injection.…”

Section: Protocolmentioning

confidence: 99%

Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake

et al. 2002

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The aims of this study were to determine the total body phylloquinone and its metabolic turnover in human subjects using a tracer dose of [5-H 3 ]phylloquinone containing 55·5 £ 10 4 MBq=mmol. Seven subjects aged 22 to 49 years were given 0·3 mg isotopic phylloquinone intravenously on a control diet (75 mg phylloquinone/d) and blood, urine and faeces were sampled periodically for 6 d. Five of these subjects were studied a second time after 3 -8 weeks on a low-vitamin K diet (8 mg/d). The changes in the radioactivity of plasma phylloquinone with time were analysed by the method of residuals and fitted to a curve composed of two exponential components. The size of the exchangeable body pool was calculated by isotope dilution. Plasma phylloquinone levels fell during vitamin K restriction but the vitamin K-dependent coagulation factors did not change. After injection the first exponential decay curve t 1/2 was 1·0 (SD 0·47) h in the subjects on the control diet and 0·49 (SD 0·27) h after vitamin K restriction. On the control diet, the second exponential t 1/2 was 27·6 (SD 124) h that did not change on the low-vitamin K diet (t 1=2 ¼ 25·1 (SD 13·5) h). These results indicate that the turnover time for phylloquinone in human subjects is about 1·5 d. Urinary excretion of 3 H-metabolites ranged from 30 % of the administered dose on the control diet to 38 % on the restricted diet and had the same turnover rate as the second component of the plasma decay curves. The exchangeable body pool of phylloquinone declined from about 1·0 mg/kg before restriction to lower values after vitamin K restriction. The faecal excretion of phylloquinone and its metabolites fell from 32 % of the administered dose on the control diet to 13 % on the restricted diet. Vitamin K: Radioactive phylloquinone: Exchangeable body pool: Metabolic turnoverGreat advances have been made in the understanding of the distribution, function and metabolism of vitamin K since its discovery by Henrik Dam. (Dam, 1935;Olson, 1999) Less well documented is the content of vitamin K in the human body and the extent of its metabolic turnover. The first attempt to measure phylloquinone turnover in human subjects was made by Shearer et al. (1972), who administered 1 mg [1 0 , 2 0 -3 H 2 ]phylloquinone (200 MBq/ mmol) intravenously to each of three young male volunteers whose plasma was sampled at intervals for 96 h. They observed that after 2 h only 10 % of the initial radioactivity remained in the plasma space, and that the decay curves over 6 h could be resolved into two exponential functions with half-times of 20-24 min and 121-150 min. Later Shearer et al. (1974) repeated their study using 45 mg-phylloquinone of higher specific activity (3515 MBq/mmol) and obtained similar results. Bjornsson et al. (1979) carried out similar turnover studies in four healthy male volunteers using 300 mg [1 0 , 2 0 -3 H 2 ]phylloquinone (3237 MBq/mmol). They also observed two exponential components to the decay curves of 26 (SD 8) min and 166 (SD 10) min over 10 h.None of these invest...

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Section: Protocolmentioning

confidence: 99%

Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake

et al. 2002

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“…It therefore seems likely that resistance to warfarin and an increased vitamin K requirement are pleiotropic effects of the same gene. When compared to warfarinsusceptible animals (Rw'Rw'), homozygous resistant (Rw 2 Rw 2 ) and heterozygous resistant (Rw'Rw 2 ) rats were found to have respectively a 20-fold and 2-fold increase in vitamin K requirement (Hermodson, Suttie & Link, 1969). Bishop, Hartley & Partridge (1977) found in the laboratory that litter sizes of F 2 (Rw'Rw 2 x Rw'Rw 2 ) matings were significantly smaller than backcross matings (Rw 1 Rw 2 x Rw1Rw l , or reciprocal) at 8 weeks of age.…”

Section: Discussionmentioning

confidence: 96%

Vitamin K deficiency syndromes in warfarin-resistant brown rats (Rattus norvegicus)

Partridge

1980

Lab Anim

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“…Some work has been conducted on that matter and there is conflicting evidence on vitamin K requirements of resistant rats. For instance, Hermodson et al (1969), Greaves and Ayres (1973) clearly showed that the Welsh resistant strain was highly dependent on high daily vitamine K (about 13 times the standard requirements) in order to maintain normal coagulation. More recently Markussen et al (2003) showed, on a Danish resistant strain, that the animals were moderately but significantly deprived of vitamin K and had higher daily requirements than susceptible individuals.…”

Section: The Norway Ratmentioning

confidence: 99%

Challenges of Anticoagulant Rodenticides: Resistance and Ecotoxicology

Berny¹

2011

Pesticides in the Modern World - Pests Control and Pesticides Exposure and Toxicity Assessment

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Warfarin metabolism and vitamin K requirement in the warfarin-resistant rat

Cited by 94 publications

References 0 publications

Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake

Total body phylloquinone and its turnover in human subjects at two levels of vitamin K intake

Vitamin K deficiency syndromes in warfarin-resistant brown rats (Rattus norvegicus)

Challenges of Anticoagulant Rodenticides: Resistance and Ecotoxicology

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