Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function.

The concentrations of quinidine, (3S)-3-hydroxyquinidine (3-OH), and 2'-oxoquinidinone (2'-OXO) in serum samples from 25 patients on long-term quinidine therapy were determined by a high-pressure liquid chromatography assay. Large individual variation in the levels of each of the compounds measured was observed. After correcting for differences in protein binding, the ratio of 3-OH/quinidine in serum water is 0.61 +/- 0.31 (SD) and the ratio of 2'-OXO/quinidine is 0.39 +/- 0.44. Seven of the 25 patients had serum water levels of one of these metabolites similar to or greater than that of quinidine. The quinidine levels, after normalizing for dose, are significantly higher in hemodialysis patients (about twice) than in nonazotemic patients; azotemic patients have mean values intermediate between them. Quinidine, 3-OH, and 2'-OXO are equally potent antiarrhythmic drugs (ED50 = 0.18, 0.17, and 0.21 mmoles/kg, respectively) when tested against chloroform- and hypoxia-induced ventricular fibrillation in mice. O-Desmethylquinidine, a new metabolite detected in urine of quinidine-treated patients, is less active. Quinidine and 2'-OXO are equally potent (ED50 = 0.010 mmoles/kg), while 3-OH seems less potent and more toxic when tested against BaCl2-induced ventricular arrhythmias in rabbits. Thus, these metabolites appear to contribute to the effects of quinidine and may make a significant contribution in some cases.

Accumulation of polyamines and their weak association with lower body temperature in elderly convalescent patients.

Because spermine and spermidine have caused hypothermia in rodent experiments, we tested the hypothesis that these polyamines accumulate in some elderly convalescent patients and that this accumulation could predispose to lower body temperature. Fourteen healthy young, seven healthy older, and 47 convalescent elderly subjects had serum spermine and spermidine concentrations measured by high-pressure liquid chromatography. The mean +/- SD spermine values were 18 +/- 10, 24 +/- 15, and 40 +/- 54 ng/ml, respectively. The values for spermidine were 28 +/- 10, 38 +/- 29, and 76 +/- 46 ng/ml, respectively. The differences between the young and convalescent elderly were statistically significant for both compounds. Rectal temperatures were measured in 39 elderly convalescent subjects with a thermometer designed for accuracy at low temperatures. These subjects were stratified into a warm and cool half based on a median rectal temperature of 37 degrees C. There was an association between having high spermine levels and being in the cool half of the elderly convalescent group (P less than 0.05). We conclude that some elderly convalescent patients have high levels of spermidine and spermine and that these high spermine levels may be associated with lower body temperature.