Control of quinidine dosage.

The usefulness of quinidine in treatment of cardiac arrhythmias is often limited by the difficulty of determining adequate dosage. When control has not been effected by small doses, the physician may be deterred from increasing these because of the risk of toxicity. The electrocardiogram does not help to indicate that this may be imminent, since the effects of overdosage (widening of QRS and ventricular arrhythmias) are preceded by the clinical evidence of intolerance-vomiting and tinnitus. In 1943 Brodie and Udenfriend described a fluorimetric method of estimating quinidine in serum. Subsequently it has been demonstrated that the therapeutic and toxic effects of the drug are related to serum concentration. Kalmanson and Sampson (1949) showed that toxic phenomena occurred more frequently with levels above 0-6 mg./100 ml. than with lower concentrations. Sokolow (1951) found that the majority of conversions from auricular fibrillation to sinus rhythm took place at levels between 04 and 10 mg./100 ml. Where such levels had not been reached, dosage could be increased with safety and with the possibility of therapeutic success. Above 1.0 mg./100 ml., the chances of conversion are only slightly enhanced, while the risk of toxicity is much increased. In the present investigation, the relationships between dosage, serum level, and therapeutic effect were studied. The urinary excretion of quinidine was studied also, and the urines were tested with potassium mercuri-iodide (Tanret's reagent) to determine whether precipitate density was any guide to serum level. Tanret's reagent has been used hitherto to detect the presence of quinine in urine, either to ensure that prophylactic doses were actually being taken, or to determine whether quinine used therapeutically was being absorbed (see Howie and Murray-Lyon, 1943; and, for a quantitative method, Lipkin and Ramsden, 1918).