Disposition kinetics of quinidine

Abstract

The disposition kinetics of quinidine in 12 hospitalized patients in whom oral quinidine therapy was to be initiated is described. Quinidine in doses of 2.6 to 5.2 mg/kg base were infused intravenously over 22 min. Plasma samples were collected during the postinfusion for 24 hr and analyzed by a specific and sensitive assay procedure. In the 12 hr after administration, postinfusion plasma quinidine concentration decay was described by a biexponential equation. Attempts to include the 24-hr data point in the fitting procedures resulted in poorer agreements between the theoretical and experimental curves. A 2-compartment open model is proposed to describe the disposition of quinidine. The volume of the central pool (Vc) and steady-state volume of distribution (Vdss) were 0.91 +/- 0.11 L/kg and 3.03 +/- 0.25 L/kg, respectively, and indicate that quinidine distribution is predominantly extravascular. Quinidine distribution was quite rapid (t1/2alpha = 7.19 +/- 0.70 min), while the apparent elimination half-life (t1/2beta) was considerably longer, 6.333 +/- 0.47 hr. Total body plasma clearance ranged from 1.49 to 7.15 ml/min/kg (mean 4.70) and is primarily associated with nonrenal mechanisms of drug elimination. Urine specimens collected for 48 hr indicated that 17% of the dose is excreted intact and that urinary excretion was essentially complete within 24 hr. Renal clearance (Clr) was 0.80 +/- 0.18 ml/min/kg. The study demonstrated that there is substantial interpatient variability with respect to quinidine disposition.

Bioavailability of quinidine in congestive heart failure.

“…However, the hepatic extraction ratio of quinidine in the non-heart failure patient is relatively low and drug clearance by this organ is therefore independent of liver blood flow. Thus, in spite of a possible decrease in hepatic blood flow in (Conrad etal., 1977;Greenblatt etal., 1977;Guentert et al, 1979;Ueda, Hirschfeld, Scheinman, Rowland, Williamson & Dzindzio, 1976;Ueda & Dzindzio, 1978), the results of this investigation demonstrated that in 15 of the 18 patients studied (83%), a single compartment model was all that was needed to characterize the absorption and disposition of orally administered quinidine. This finding is completely in agreement with the rapid a-phase seen after intravenous quinidine (Conrad et al, 1977;Greenblatt et al, 1977;Guentert et al, 1979;Ueda & Dzindzio, 1978) and the recent suggestion by Guentert et al (1979) that for individualized dosage adjustments, application of the one-compartment model is adequate.…”

Effect of Propranolol on Pharmacokinetics and Acute Electrocardiographic Changes following Intravenous Quinidine in Humans

“…Previous pharmacokinetic studies of quinidine indicate that its total clearance gener ally falls between 3 and 7 ml/min/kgin healthy volunteers; from 15 to 40% of total clearance is accounted for by renal clearance of the un changed compound (4,10,11). Therefore, the hepatic extraction ratio for quinidine appears to be considerably less than 50%, and changes in hepatic flow would not be expected to have a substantial effect upon its extrarenal clear ance.…”

Comparison of quinidine plasma concentration curves following oral administration of some short‐ and long‐acting formulations.

“…Therefore, in order to limit the risks of serious toxic reactions when the therapeutic range is overcome, individualization of quinidine therapy by means of plasma levels monitoring is often recornmended (Kessler, 1974). Due to the short half life of the drug , Ueda, Hirschfeld, Scheinman, Rowland, Williamson & Dzindzio, 1976 rapidly absorbed formulations such as quinidine sulphate must be administered every 4-6 h. In our experiments, following single oral doses of quinidine sulphate plasma levels rose rapidly, peaked after 2.25 h and then fell off with an exponential decline. These findings are in agreement with previous results Goldberg & Chakrabarti, 1964;Kalmansohn & Sampson, 1950).…”