Tolbutamide Dicoumarol

Dicoumarol inhibits the metabolism of tolbutamide and increases its effects cases of hypoglycaemic coma have been reported. Chlorpropamide may be affected similarly. Although isolated cases of interactions (raised prothrombin times, bleeding or hy-poglycaemia) have been seen in patients taking sulfonylureas and coumarins, in general, no important interaction appears to occur. There also appears to be no interaction between phenindione and tolbutamide. 

Dicoumarol. Dicoumarol has been shown to increase the serum levels of tolbutamide, prolong its half-life (more than threefold), and reduce blood-glucose levels in both diabetics and healthy subjects. This may become excessive in a few patients and hypoglycaemic coma has been described in 3 diabetics, and one non-diabetic. ... 

Dicoumarol appears to increase the effects of tolbutamide by inhibiting its metabolism by the liver. This may also be true for chlorpropantide. The increase in the anticoagulant effects of dicoumarol by tolbutamide may, in part, be due to a plasma protein binding interaction. In the case of phenprocoumon there seem to be several different mutually opposing processes going on, which cancel each other out. There is no clear explanation for most of these interactions. 

Kristensen M, Hansen JM Potentiation of the tolbutamide effect by dicoumarol. Diabetes (1967)16,211-14. 

Jahnchen E, Meinertz T, Gilfrich H-J, Groth U. Phaimacokinetic analysis of die interaction between dicoumarol and tolbutamide in man. EurJClin Pharmacol 916) 10, 349-56. 

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