The interaction of the anticoagulant drug warfarin and its metabolites with human plasma albumin was studied by equilibrium dialysis. A 20-fold variation of buffer ionic strength (0.017-0.340) caused no significant change in the warfarin association constant. But the binding strength rose significantly as the pH was increased from 6.0 to 9.0 and then declined at pH 10.0. The 6-, 7-, and 8-hydroxywarfarin metabolites showed a 7- to 23-fold reduction in binding strength at pH 10.0. These ...

Cimetidine potentiates the anticoagulant effect of warfarin sodium, but in one small study ranitidine hydrochloride did not. Furthermore, these drugs have not been compared in the same subjects. Eleven normal subjects received single oral doses of 1.5 mg/kg racemic warfarin sodium alone, with cimetidine (1,200 mg/day orally), or with ranitidine (300 mg/day orally), beginning three days before the warfarin and daily thereafter for the duration of hypoprothrombinemia. Blood samples were ...

Because of the known interaction of warfarin and disulfiram and the "disulfiram effect" of metronidazole, the interaction with metronidazole of commercial racemic warfarin and its separated enantiomorphs was evaluated in eight normal subjects. Single oral doses of racemate, S(-)-warfarin, and R (+)-warfarin, were administered in the amounts of 1.5, 0.75 and 1.5 mg per kilogram of body weight, respectively, with and without metronidazole, 750 mg by mouth, beginning seven days before the ...

The hyperviscosity syndrome is an uncommon complication in IgG myeloma. Its occurrence has been ascribed to the presence in the serum of high molecular weight polymers of the IgG proteins. Three patients with IgG myeloma and the clinical hyperviscosity syndrome were investigated, none of whom had IgG polymers in the serum by analytical ultracentrifugation. Relative serum viscosity in these patients ranged from 10 to 17.4 (normal 1.4-1.8). The total serum proteins ranged from 14 to 19 ...

In this second reported kindred of hereditary resistance to oral anticoagulant drugs the propositus required 75 to 80 mg of sodium warfarin a day (25 standard deviations above the average dose) to achieve hypoprothrombinemia in the therapeutic range. With this dose, the hypoprothrombinemia could be corrected with daily doses of vitamin K1 of as little as 0.125 mg. Seventeen other family members had an equally resistant response to the oral anticoagulant drugs. The metabolism of sodium ...

To compare the marked hypoprothrombinemic augmentation in man of racemic warfarin sodium by the pyrazolons phenylbutazone and sulfinpyrazone with that of the coumarin anticoagulant phenprocoumon, these interactions were studied prospectively in six normal subjects. Large single doses of racemic phenprocoumon, 0.6 mg/kg orally, were administered with and without daily phenylbutazone, 300 mg, or sulfinpyrazone, 400 mg, beginning three days before phenprocoumon and continuing for 14 days. ...

The article on antithrombotic therapy1 that appeared in the January 23, 1995, issue of the Archives was introduced as a synopsis of the proposed guidelines for an American College of Chest Physicians Consensus Conference on Antithrombotic Therapy, including recent updates and information that will likely influence future recommendations. The authors recommend reversing the anticoagulant effects of warfarin when the international normalized ratio is between 6.0 and 10.0 and "the patient ...

The relationship between the in vitro dissolution kinetics and the in vivo intestinal absorption characteristics of tablet preparations of the coumarin anticoagulant warfarin has been studied. The composition of the dissolution medium had a significant quantitative and qualitative effect on dissolution kinetics. Warfarin absorption in man varied with respect to lag time, absorption rate constants, and the type of kinetics observed. These variations may result from variable gastric ...

Because daily ingestion of 592 mL of table wine (12% ethanol by volume) during mealtime had no notable effect on long-term, "therapeutic" hypoprothrombinemia with racemic warfarin sodium in normal subjects, similar experiments were repeated using fortified wine (20% ethanol by volume) during fasting. For 21 days, seven normal subjects were given therapeutic levels of the anticoagulant racemic warfarin alone and with warfarin plus 296 mL/day of fortified wine during fasting. The ...

PRIMARY macroglobulinemia is a systemic disease of many manifestations.1 One of the common complications of the disease is a syndrome consisting of bleeding and ocular and neurologic disorders attributable to hyperviscosity of the blood. The syndrome can be fatal, but with control of the serum macroglobulin level and the hyperviscosity many of the patients show striking clinical improvement.2,3This report describes a case of macroglobulinemia in which an extraordinary increase in the ...