The absolute bioavailability of quinidine was studied in 11 hospitalized patients. A 400-mg dose of quinidine gluconate was administered to each patient by intravenous infusion and as an oral solution. Drug treatments were separated by a 72-hr period. In 8 patients, peak plasma quinidine concentrations were reached in 65 min after the oral dose; in the remaining 3 subjects, peak concentrations were reached later. From the ratio of the total area under the plasma concentration-time curves (AUCoral/AUCir), the absolute bioavailability of quinidine ranged from 44% to 89% (mean, 72). In 8 patients, the ratio of the total amount of quinidine excreted in the urine in 48 hr (AUinfinity oral/AUinfinity ir) indicated that the extent of quinidine bioavailability varied form 47% to 96% (mean, 73). The predicted bioavailability of quindine due to first-pass effects was 76+/-11%. It is concluded that absorption after the oral solution was rapid and that the reduction of quinidine bioavailability was due to first-pass hepatic drug removal.
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.
The pharmacokinetics of quinidine was studied in cardiac patients with and without congestive heart failure. Following intravenous drug infusion, plasma and urine samples were collected at various times and analyzed for quinidine by a specific assay procedure. Although plasma quinidine concentrations varied over a wide range in both patient groups, the mean drug concentration at each time point was always higher in the congestive failure patients. In the 24‐hr postinfusion period, plasma drug disposition was biexponential with half‐life values for the fast and slow disposition processes (t½α and t½β) similar for each group. The respective values of t½α and t½β were 5.6 min and 6.8 hr in the congestive heart failure patients and 6.1 min and 6.2 hr in the control group. The volume of the central pool (Vc) and Vdarea were smaller in the congestive heart failure group (p < 0.05) with values of 0.44 ± 0.12 and 1.81 ± 0.49 L/kg, respectively, compared with those of the control group of 0.75 ± 0.31 and 2.67 ± 1.17 L/kg. Total body plasma drug clearance (Cl) was also lower in the heart failure patients (p < 0.05). The estimated Cl values were 3.16 ± 1.10 and 4.95 ± 1.36 ml/min/kg for the heart failure and control patients, respectively. Renal quinidine excretion accounted for 15% and 18% of the administered doses and corresponded to renal clearance values of 0.48 ± 0.15 and 0.95 ± 0.56 ml/min/kg in congestive heart failure and control patients, respectively. The results of this study indicate that the higher quinidine concentrations observed in congestive heart failure patients are due to a significantly smaller distribution volume for the drug.
Serum disopyramide determinations and 24-hour Holter monitoring were performed in 20 cardiac subjects with ventricular premature contractions (VPCs) after the first, seventeenth, and thirty-seventh doses of disopyramide, 100 mg (10 subjects; low-dose group) or 200 mg (10 subjects; high-dose group) every 6 hr for 10 days to assess the ability of single- or first-dose data to predict serum disopyramide concentrations at steady state and the relationship between steady-state serum disopyramide concentrations and VPC suppression. Control Holter recordings were made for 48 hr in each subject. There were strong correlations in both groups between data for the AUC over 0 to 6 hr for the first dose (AUC60) and average (C ss) and trough (C min) steady-rate serum disopyramide concentrations after the seventeenth and thirty-seventh doses and the two combined. C ss and C min were related to AUC60 by the following expressions for both dosage groups: C ss = 0.22 AUC60 + 0.90 and C min = 0.20 AUC60 + 0.70. There were good correlations between 6-hr serum disopyramide concentration after the first dose and C ss and C min. There was strong correlation between overall average steady-state serum disopyramide concentration and suppression of VPC frequency. The relationship between VPC suppression and overall average trough serum disopyramide concentration at steady state, on the other hand, was weak.
The perplexing clinical course of a 23-year-old black male with isolated gonococcal pulmonary valvular endocarditis is presented. M-mode echocardiography provided the first clue to the presence of pulmonary valvular vegetations and the proper diagnosis. Since Neisseria gonorrhea appears to have a particular affinity for the pulmonary valve, the presence of isolated pulmonary valvular endocarditis should raise the strong possibility that Neisseria gonorrhea is the offending organism. This case report of pulmonary valvular vegetations detected by echocardiography strongly emphasizes that all four cardiac valves must be visualized in order to rule out the presence of echocardiographically detectable valvular vegetations.
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