Biochemical changes associated with intractable pain.

from Schwartz-Mann and Clinical Assay (the results with these two kits showed close correlation). Steady-state plasma quinidine concentrations ranged from 4-2 to 127 ,umol/I (1-3 to 3-8 lg/ml) with an average of 7 0 ,umol/I (2-1 ,ug/ml). All 12 patients showed a rise in plasma digoxin concentrations when quinidine was given (mean value 1-1 nmol/l (0-85 ng/ml) before quinidine, and 2-0 nmol/l (1-6 ng/ml) after quinidine). Five determinations of plasma digoxin were made in each patient after the start of quinidine treatment. One of the six patients whose plasma concentrations rose above the therapeutic range on one or more occasions developed symptoms of digitalis intoxication. In the first four patients the digoxin concentration was measured only once before adding quinidine, whereas more determinations were performed in the remaining patients to check that they had been taking the tablets as prescribed and that the digoxin concentrations represented steady-state values. The figure shows the drug concentration curves in the patient whose concentrations were measured most often. The possibility of interference by quinidine or a metabolite of quinidine in the digoxin assay was excluded by the following control studies. (1) Digoxin was sought in the plasma of patients undergoing cardioversion in the same way while not on digoxin treatment: no measurable concentrations were found. (2) Quinidine was added to samples of whole blood from patients on digoxin alone until the quinidine concentrations fell within the therapeutic range: this did not affect the digoxin concentrations. (3) Digoxin added to blood samples from one group of patients who were taking quinidine alone, and from another group of patients not taking quinidine: the digoxin concentrations did not differ between the two groups.