No abstract

Potentiation of the anticoagulant-effect of warfarin by amiodarone was studied in 30 patients. Thirteen received both drugs concurrently, and 17 received warfarin alone and the combination sequentially. Warfarin doses were adjusted to maintain the prothrombin time between 25-30% of control and its kinetics were compared to those in 20 control patients who received warfarin alone. Potentiation occurred in 28/30 patients, presenting as a 35%-65% reduction in the required dose of warfarin, and was correlated with the dose of amiodarone (r = 0.77, p less than 0.01). The free warfarin fraction was not affected by amiodarone (1.8% vs 1.6% in the controls). Warfarin clearance was lower in amiodarone-treated patients than in the controls (1.4 vs 3.1 ml/min, p less than 0.01) with similar plasma concentrations (1.5 vs 1.2 micrograms/ml) despite administration of lower doses (23.3 vs 39 mg/week respectively). The amiodarone concentration was significantly correlated with the warfarin concentrations independent of the effect of amiodarone on the dose of warfarin. Amiodarone hat no effect on prothrombin other than through its actions on the dose and plasma concentration of warfarin. The mechanism of the amiodarone-warfarin interaction is pharmacokinetic through dose - and concentration - dependent inhibition of warfarin elimination.

Antithyroid drugs, considered the treatment of choice for hyperthyroidism during pregnancy, may have an adverse effect on intellectual development of the offspring. We examined the intellectual capacity of 31 subjects aged 4-23 years, born to women with Graves disease who received antithyroid drugs throughout pregnancy. Methimazole 40-140 mg/week (n = 15) or propylthiouracil 250-1400 mg/week (n = 16) was given. I.Q. was assessed using the Wechsler test appropriate for age. Twenty-five unexposed siblings served as controls. The exposed and unexposed groups did not differ with respect to the total I.Q. Both groups scored equally in verbal and performance skills and in each of six main subcategories of the tests. There was no difference between exposure to methimazole and propylthiouracil or between the higher (greater than 40 mg/week and greater than 600 mg/week, respectively) and lower dosages. All children were euthyroid at birth and none had goitre. We conclude that exposure to methimazole or propylthiouracil during pregnancy in doses sufficient to control maternal hyperthyroidism does not pose any threat to intellectual capacity of the offspring.

3bound to the membrane (in that it resists washing out by the normal flow of secretions). A firmly bound effect was therefore sought by exposing normal red cells to saliva for 5 min, and then washing, before measuring ouabain-insensitive efflux. Table 2 shows that there was no difference between cells exposed to saliva and then washed, and cells not exposed to saliva. No firmly bound factor was demonstrated.The significance of humoral substances affecting membrane transport remains to be clarified. There does not appear to be any known hormone, for example, which could easily explain the above effect of saliva, whereas simple physical or physicochemical factors would seem to be excluded by the experimental controls. Modification of the cell membrane by uncharacterized circulating or secreted factors may have a bearing on transport processes in general, and possibly on the disturbance of CF in particular. However, the red cell model, as used in this study, has not confirmed that such a mechanism is important in CF. CONCLUSIONIn a preliminary study, the red blood cells of patients with cystic fibrosis were found to show decreased ouabain-insensitive Na+ efflux. The ouabain-sensitive Na+ efflux, total Na+ efflux, and Na+ influx were found to be normal. This information was used to guide the choice of transport parameters in the main study. The effect of cystic fibrosis saliva on normal red cells was not significantly different from that of control saliva, but both Pediat. Res. 12: 3-6 (1978) normal saliva and cystic fibrosis saliva appear to contain a substance which accelerates Na+ transport in the red cell.