Single and Multiple Dose Pharmacokinetics of Oral Quinidine Sulfate and Gluconate HERMANN R. OCHS, MD DAVID J. GREENBLATT, MD ELAINE WOO, MD KATE FRANKE HENRY J. PFEIFER, RPh THOMAS W. SMITH. MD zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Boston, Massachusetts From the Clinical Pharmacology Unit, Massa- chusetts General Hospital; the Cardiovascular Division, Department of Medicine, Peter Bent Brigham Hospital; and the Department of Medi- cine, Harvard Medical School, Boston, Massa- chusetts. This study was supported in part by Grant HL-18003 from the U.S. Public Health Service, Bethesda, Maryland (Dr. Smith), and by a grant from Cooper Laboratories, Inc., Cedar Knolls, New Jersey. Dr. Ochs was supported by Deutsche Forschungsgemeinschaft, Bonn-Bad Godesberg, West Germany. Dr. Smith was an Established In- vestigator of the American Heart Association. This work was done in part during the tenure of a re- search grant-in-aid award (no. 13-506-756) from the American Heart Association, Western Mas- sachusetts Division and the American Heart As- sociation, Massachusetts Affiliate, Inc. Boston, Massachusetts (Dr. Greenblatt). Manuscript received September 15, 1977, accepted October 5, 1977. Address for reprints: David J. Greenblatt, MD, Clinical Pharmacology Unit, Massachusetts General Hospital, Boston, Massachusetts 02114. The pharmacokinetics of oral quinidine sulfate and quinidlne gluconate were compared in seven healthy volunteers in a two part pharmacoklnetlc study. Part I was a single dose crossover trial assessing absorption and elimination of quinidine sulfate (400 mg, equivalen?to 331 mg of quinidine base) and quinidine gluconate (495 mg, equivalent to 309 mg of quinidlne base). Mean kinetic values for the sulfate and gluconate preparations, respectively, were: peak serum quinidine level 2.07 versus 1.24 hg/ml (P KO.025); time of peak concentration 1.61 versus 3.64 hours after the dose (P <0.02); first order absorption half-life 41.1 versus 61.2 minutes (P COO.1); elimination half-life 6.1 versus 6.3 hours (difference not sig- nificant); absolute systemic availability (based upon comparison with intravenous data from the same subjects) 66.0 versus 76.5 percent (dif- ference not significant ) using area under the serum concentration curve, or 63.7 versus 73.6 percent (P <0.05) using cumulative 46 hour urinary excretion of qulnktine. The findings indicate that absorption of quinidine gluconate is slightly less complete but much less rapid than that of quin- idine sulfate. Part II evaluated steady state kinetics of both preparations in a cross- over trial in the same subjects. Maintenance dosing schedules were 200 mg of quinidine sulfate every 6 hours versus 495 mg of quinidine gluconate every 12 hours. Systemic availability of the gluconate at the steady state level was IO percent less (based upon area under the serum concentration curve) or 7 percent less (based upon urinary excretion of quinidine) than that of the sulfate, but the differences were not significant. Interdose fluctuation in serum quinidine concentrations during the gluconate trial averaged 70 percent, which was not significantly different from the av- erage of 67 percent during the sulfate trial. However, variation within and between subjects in minimal steady state levels with quinidine gluconate (15.6 and 16.0 percent, respectively) was greater than with quinidine sulfate (7.2 and 9.9 percent, respectively). Steady state concentrations during the multiple dose trial were not accurately predicted from single dose pharmacokinetics, either for quinidine sulfate (r = 0.45) or qulnidine gluconate ( f = -0.12), but deviation of observed from predicted con- centrations tended to be greater with quinidine gluconate. The slow ab- sorption of quinidine from the gluconate preparation allows maintenance therapy on a 12 hourly dosage schedule with acceptable interdose fluc- tuation in serum levels. Variability within and between subjects in ab- sorption kinetics tends to be greater with quinidine gluconate than with the more rapidly absorbed sulfate salt. Patient compliance is an important consideration during long-term ant&rhythmic therapy of ambulatory patients. Clinicians must choose not only the correct antiarrhythmic agent but also the dosage form and dosing schedule that are likely to maximize compliance. The need for multiple daily doses is an important drawback to the use of the quinidine 770 April 1979 The American Journal of CARDIOLOGY Volume 41