Individual variation in the response to phenprocoumon

Husted, S.; Andreasen, F.

doi:10.1007/bf00566532

Cited by 11 publications

(7 citation statements)

References 18 publications

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“…Furthermore, dynamic analysis of the response to acute doses of warfarin or phenprocoumon in volunteers (Nagashima et al, 1969) or patients (Husted & Andreasen, 1977) revealed inter-individual differences in the relationship between plasma inhibitor concentration and the suppression of the clotting factor synthesis. Hence, inter-individual differences in the dynamics of the coagulation homeostasis must exist.…”

mentioning

confidence: 99%

Vitamin K metabolism and vitamin K1 status in human liver samples: a search for inter‐individual differences in warfarin sensitivity

Thijssen

Drittij-Reijnders

1993

Br J Haematol

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Vitamin K-dependent parameters in human liver samples were investigated to find a clue to the inter-individual differences in sensitivity for oral anticoagulants. Vitamin K epoxide reductase and vitamin K-dependent carboxylase activity differed 2-3-fold between the samples. Microsomal warfarin binding correlated significantly with the reductase activity. Microsomal vitamin K epoxide reductase of the different samples showed equal sensitivity for warfarin inhibition, I50 about 0.1 microM. Vitamin K epoxide reductase activity stimulated by NADH/lipoamide and microsomal lipoamide dehydrogenase activity showed higher inter-subject variability than the reductase activity by itself. Liver vitamin K1 levels varied 4-5-fold. Total and liver microsomal vitamin K1 levels were correlated. One of the liver samples was obtained from a donor anticoagulated with phenprocoumon and additionally treated with vitamin K1. High levels of the vitamin and its epoxide were present. Phenprocoumon was essentially irreversibly bound to the microsomes. In general the results confirm inter-individual differences in the hepatic vitamin K-dependent systems; the differences as such were found to be small. However, as the various parameters can work synergistically in the same direction, they may well account for the wide dose range observed in oral anticoagulant therapy.

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confidence: 99%

Vitamin K metabolism and vitamin K1 status in human liver samples: a search for inter‐individual differences in warfarin sensitivity

Thijssen

Drittij-Reijnders

1993

Br J Haematol

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“…A change in the affinity for coumarin drugs at the 'receptor site' in the liver has been suggested (Husted et al, 1976) as the cause of the increased sensitivity to phenprocoumon during methyltestosteron therapy. This mechanism as well as an increase in the degradation rate of coagulation factors, which was recently observed in patients with acute myocardial infarction (Husted & Andreasen, 1976b), are possible alternative explanations to that of the altered pharmacokinetics suggested above.…”

Section: Discussionmentioning

confidence: 70%

“…There is a trend towards a more intensive therapy (more PP%'s below 10 and fewer above 25) of patients aged 61-70 years than in those between 50-60 years. This tendency is, in particular, pronounced for phenprocoumon, which has a high potency and a long biological half life in plasma (Husted & Andreasen, 1976b). Considering the whole patient population, there is a statistically significant difference (2 = 14.75, P < 0.001) between the levels of the PP%'s in patients in the age groups 50-60 years and 61-70 years.…”

Section: Resultsmentioning

confidence: 93%

“…This mechanism as well as an increase in the degradation rate of coagulation factors, which was recently observed in patients with acute myocardial infarction (Husted & Andreasen, 1976b), are possible alternative explanations to that of the altered pharmacokinetics suggested above. Hewick, Moreland, Shepherd & Stevenson (1975) compared the pharmacokinetics and the pharmacodynamics of warfarin in six elderly patients and in four healthy younger volunteers.…”

Section: Resultsmentioning

confidence: 96%

“…Phenprocoumon has a long biological half life (Husted & Andreasen, 1976b) and a negligible excretion as unchanged drug (Glogner & Heni, 1973). It might be suggested that reduced rates of elimination of the coumarin drugs are important factors in the reduced requirement and the increased effect of these drugs in advanced age.…”

Section: Resultsmentioning

confidence: 99%

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The influence of age on the response to anticoagulants.

Husted¹,

Andreasen²

1977

Brit J Clinical Pharma

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1 A group of 114 patients on long‐term anticoagulant therapy was studied. The daily maintenance dose of both phenprocoumon, bishydroxycoumarin and warfarin was found to be significantly lower in patients aged between 61 and 70 years than in the those between 50 and 60 years of age. The mean daily dose of bishydroxycoumarin, hower, when expressed on a weight basis, was not significantly lower in the elderly. 2 For bishydroxycoumarin but not for phenprocoumon and warfarin there was found a statistically significant correlation between the daily maintenance dose and the weight of the patient. 3 The mean daily dose of both bishydroxycoumarin and warfarin was 30‐40% lower than that recommended in the literature. 4 ‘Correction’ was made for potential drug interference by excluding patients in continuous medication with order drugs known to influence the treatment with orally administered anticoagulants. The interindividual variation in dosage requirements of coumarin drug was thereby reduced in the age groups above 60 years. 5 The level of vitamin‐k dependent coagulation factors, measured by Owren's ‘P and P’ method (PP%) was significantly lower (P less than 0.001) in patients of advanced age (between 61 and 70 years) than in younger patients (between 50 and 60 years). 6 The plasma concentration of albumin was significantly lower in patients over 60 years than in those under that age. 7 Correlation (P less than 0.01) was found between the daily maintenance dose of phenprocoumon and the plasma concentraction of albumin.

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