The Effect of Quinidine on Digoxin Clearance

BACKGROUND: Quinidine appeared to increase serum digoxin levels when given with quinidine. Therefore elevated serum digoxin concentrations and clinical toxicity have been reported in patient receiving quinidine. Currently, Bayesian method which estimates the most probable parameters of the drug for each patient from population parameters data is useful approach for adjusting digoxin dosage. To increase the accuracy of Bayesian method, it is desirable to use population parameters of Korean. Therefore we evaluated the effect of quinidine on digoxin clearance in Korea. METHOD: Patient's records from 19 adult cardiac disease without CHF having normal renal and liver function from Seoul National University of Hospital respectively wre evaluated. Digoxin pharmacokinetic parameters, CL and Vd, were obtained from serum concentration of digoxin of single and combined therapy at each steady-state by using bayesian method. RESULTS: This study show that quinidine reduced the total body clearance of digoxin from 2.39+/-0.17 to 1.51+/-0.08ml/min/kg(p<0.05) and reduced the digoxin volume of distribution from 8.57+/-0.29 to 4.98+/-0.19L/kg(p<0.05). This results show that digoxin dosage reduced to 40-50% in Korean, if quinidine therapy is initiated.

Arterial and Venous Differences of Thiopental Pharmacokinetics as an Intravenous Anesthesia Induction Agent and its Pharmacodynamic Inplication / 대한마취과학회지

The arterial and venous differences of thiopental. pharmacokinetics and its impact on the onset of pharmacologic effect were examined in 6 male surgical patients with normal renal and hepatic functions during short time period of 6hrs post-intravenous bolus injection over 5 second(5 mg/kg). Arterial and venous blood samples were withdrawn from radial artery and subclavian vein, respectively at the time of right before and after injection(0), 5, 10, 20, 30, 45 (sec), l, 2, 5, 10, 30(min), 1, 2, 3, 4, 5, 6(hrs). Serum concentrations of thiopental were determined by reverse-phase, high performance liquid chromatography and the clinical endpoint of anesthesia induction were interpreted as the time of loss of consciousness by observing spontaneous closing of eyes and loss of eyelash reflex. As the results, significant differences between arterial and venous concentrations were noted during early phase lasting up to 10 minutes. Arterial data was best fitted to tri-exponential decay model. In analysing pharmacokinetic parameters with serum data of 6 hrs duration, there were no significant differences in AUCo-(area under curve), AUCO-t, and clearance(P <0.05), but significant difference in peak concentrations(arterial: 103.97+/-12.15, venons:17.487+/-5.206ug/ml), and times to peak(arterial: 0.67+/-0.037, venous: 1.653+/-0.712min), AUMC O-t, MRT (mean residence time), apparent T 1/2(terminal half-life) and apparent Vdss(steady-state volume of distribution). Spontaneous eye closures were observed within 20 seconds(10-20sec) after the end of injection where arterial concentrations were at peak(n=3) or right after peak(n=3) and otherwise, venous concentrations were at low or even almost at zero(n=3), reflecting the fact that arterial eoncentrations are directly correlated to the clinical efficacy and more important in pharmaco-kinetic and dynamic aspect of drug.