Effect of food on enteral absorption of quinidine.

Abstract

Eight healthy subjects took single 400-mg doses of quinidine sulfate in the fasting state, and immediately after a standard breakfast, in a crossover study with at least 1 wk intervening. No other food or liquid was taken for 3 hr after the quinidine. Total and unbound quinidine levels were determined in multiple serum samples and in all urine collected for 48 hr thereafter. Mean systemic availability of quinidine in fasting and postprandial states based on area under the serum concentration curve (19.0/19.1 μg/ml × hr), or on cumulative urinary excretion (85.3/90.8 mg), did not differ. Compared with the fasting state, postprandial doses led to lower peak total serum quinidine levels (1.96/1.73 μg/ml) reached later after the dose (1.47/2.41 hr) and longer absorption half-life (½) (31.6/37.7 min) but none of these differences was significant. Actual differences were, in fact, considerably greater because of lower protein binding in the fasting (27.5% unbound)/postprandial (23.2%/unbound) state (p < 0.05). Peak unbound quinidine levels averaged 34% lower (0.65/0.43 μg/ml, p < 0.1), and were reached later (1.26/2.75 hr after dose, p < 0.025) in the postprandial trial. Thus, administration of quinidine with a standard breakfast did not influence total systemic availability but slowed the appearance in serum of unbound quinidine, partly due to increased serum protein binding in the postprandial state. This may explain the lower frequency and severity of quinidine-attributed side effects (nausea, diarrhea, nasal congestion, and palpitations) in the postprandial trial. Clinical Pharmacology and Therapeutics (1980) 27, 188–193; doi:10.1038/clpt.1980.29