Serum disopyramide concentrations and suppression of ventricular premature contractions.

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.

Relationship between saliva and serum quinidine concentrations and suppression of ventricular premature beats.

Saliva and serum quinidine concentrations were determined in six cardiac patients after twice-daily dosing with 324 or 648 mg quinidine gluconate and the relationship of these concentrations to the degree of suppression of ventricular premature beats (VPB) was evaluated. Mixed saliva and corresponding serum samples were obtained at various times after the 1st, 9th, and 19th doses. With serum quinidine concentrations ranging from 0.05 to 0.83 micrograms/ml after the first dose, the average saliva/serum ratios for quinidine varied between 0.25 and 1.35 (0.54 +/- 0.43). At steady state with the serum quinidine concentrations ranging between 0.36 and 3.35 micrograms/ml, the average saliva/serum ratios ranged from 0.27 to 1.79 (0.81 +/- 0.72) and from 0.19 to 1.84 (0.90 +/- 0.85) for the 9th and 19th doses, respectively. The interpatient variations in the saliva/serum ratio were large for the three doses (approximately 90%). On the other hand, the intrapatient variations were smaller and diminished with each succeeding sampled dose (from 31 to 18 to 12% for the 1st, 9th, and 19th doses, respectively). Moreover, the value for the quinidine saliva/serum ratio for a given patient was similar for all three doses. No significant correlation between the extent of VPB suppression and the concentrations of quinidine in the saliva or serum was observed. The data suggest that salivary quinidine concentrations may be clinically useful to monitor serum drug concentrations in a given patient. However, the relationship between saliva and serum quinidine concentrations and suppression of VPB measured by Holter monitoring is not clear-cut.

Bioavailability of quinidine in congestive heart failure.

1 The oral bioavailability of quinidine was evaluated in eight patients with moderate to severe congestive heart failure. Each patient was given a 400 mg dose of quinidine gluconate by intravenous infusion and orally in solution. Serial plasma samples and total urine for drug analysis were collected for 24 and 48 h after drug administration, respectively. 2 When compared to control cardiac patients, the rate of quinidine absorption was slower in the heart failure patients. The mean value for the apparent absorption half-life and time to achieve peak plasma quinidine concentration was 38 +/- 18 min and 2.4 +/- 1.5 h respectively. The corresponding values observed in the control subjects were 18 +/- 6 min and 1.0 +/- 0.6 h. 3 The extent of quinidine absorption when evaluated by the AUC and urinary excretion methods was about 72% of the administered dose in the congestive heart failure patients. This value was similar to the extent of quinidine absorption (approximately 73%) observed in the control subjects. 5 When compared with non-heart failure cardiac patients, the results of this study suggest that patients with congestive heart failure may require smaller oral quinidine dosages to achieve therapeutic drug concentrations in the plasma or serum.

Clinical decision-making with treadmill testing and thallium 201.

Fifty patients were prospectively evaluated for myocardial ischemia utilizing treadmill testing and thallium-201 imaging. By coronary angiography, 43 had significant coronary stenosis and seven were normal. The sensitivity, specificity, accuracy and predictive value of treadmill testing alone (81 per cent, 71 per cent, 80 per cent and 95 per cent) did not statistically differ from that of thallium-201 imaging (70 per cent, 86 per cent, 72 per cent and 97 per cent). Combined treadmill testing and thallium-201 imaging (84 per cent, 71 per cent, 80 per cent and 98 per cent) did not significantly affect the results of treadmill testing alone. Thallium-201 imaging failed to identify a number of patients with high risk lesions. The high prevalence of disease, the presentation of typical angina, preselection bias, multiple lead monitoring and exclusion of patients with abnormalities on the resting electrocardiogram probably accounted for failure of thallium-201 imaging to improve the results obtained with treadmill testing. The use of thallium-201 imaging in certain subsets of patient (resting electrocardiographic abnormalities, nondiagnostic treadmill testing, atypical chest pain or asymptomatic patients with abnormalities on treadmill testing) may be of value. However, the use of thallium-201 imaging as a routine screening procedure for myocardial ischemia in patients with typical angina, without due consideration of the prevalence of the disease in the population, is not justified.

Pharmacokinetics of dihydroquinidine in congestive heart failure patients after intravenous quinidine administration.

The pharmacokinetics of dihydroquinidine were studied in 8 patients with congestive heart failure following a 22 min intravenous infusion of a quinidine preparation that contained 5.9% dihydroquinidine as an impurity. Using a thin layer chromatography-fluorometric assay procedure for dihydroquinidine, the post-infusion plasma dihydroquinidine concentrations declined biexponentially. The half-life of the fast and slow dispositional processes was 4.42 +/- 1.81 min and 6.52 +/- 2.40 h, respectively. The central compartment volume for dihydroquinidine in these patients was 0.44 +/- 0.11 l/kg with an overall apparent volume of distribution of 1.14 +/- 0.38 l/kg. The computed values of total body plasma clearance of dihydroquinidine ranged from 1.29 to 2.69 ml/min/kg with a mean value of 1.94 +/- 0.60 ml/min/kg. In these patients, approximately 16% of the administered dihydroquinidine dose was excreted intact into the urine in 48 h. The estimated value of renal clearance was 0.314 +/- 0.129 ml/min/kg. When compared to control cardiac patients, the data showed that the apparent volume of distribution for dihydroquinidine is smaller in patients with congestive heart failure and as a result of this diminished volume, the clearance rate of dihydroquinidine was slower. The net effect of these differences was the production of higher plasma concentrations of dihydroquinidine in the heart failure group.

Isolated gonococcal pulmonary valve endocarditis: diagnosis by echocardiography.

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.

Temporary transvenous cardiac pacemaking in rural family practice.

Interested family physicians with proper training and minimal extra equipment can now employ transvenous pacemaking. Some cardiac centers have developed training programs for general internists and family physicians. We believe that this valuable procedure can, with proper physician training, be offered to patients in rural areas as well as in cardiac centers. While the number of patients in this rural family practice who require this procedure has not been great (ten patients in four years), the need is often urgent when it does occur. Use of this treatment modality with consultation in a 44-bed hospital was found to be safe and practical, although sometimes technically difficult. This paper describes the training, techniques used, results, and complications in a rural community in southeastern Nebraska. It is suggested that every hospital caring for seriously ill cardiac patients should have at least one physician trained to perform this emergency procedure.

Absolute quinidine bioavailability.

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.

Disposition kinetics of dihydroquinidine following quinidine administration.

The disposition kinetics of dihydroquinidine, a known impurity in drug grade quinidine, was studied in 7 patients who were hospitalized for control of cardiac arrhythmias. Quinidine gluconate injection containing 5.4 to 6.2 percent dihydroquinidine was used. Following an overnite fast, dihydroquinidine doses of 0.16 to 0.31 mg/kg base were infused intravenously over 22 min. Plasma samples were collected at various times for 12 hr and analyzed for dihydroquinidine by a thin layer chromatography-fluorometric assay procedure. Postinfusion plasma dihydroquinidine concentration decline was described by a biexponential equation which suggested that the impurity distributes within the body in two kinetically distinguishable pools. The volume of the central pool (Vc) and steady-state volume of distribution (Vdss) were 0.67 +/- 0.15 L/kg and 2.76 +/- 0.63 L/kg, respectively. The halflife of the fast (t1/2alpha) and slow (t1/2beta) disposition processes were 4.71 +/- 0.26 min and 5.71 +/- 1.00 hr. Total plasma clearance was 4.17 +/- 0.68 ml/min/kg. Renal excretion of intact dihydroquinidine accounted for 16 percent of the administered dose. The corresponding value for renal dihydroquinidine clearance (Clr) was 0.61 +/- 0.08 ml/min/kg. The results of this study indicated that there were no significant differences in the distribution and elimination characteristics of dihydroquinidine and quinidine.

Swinging heart syndrome with predominant anterior pericardial effusion.

A 16 year old male with carcinoma of the anterior mediastinum developed pericardial tamponade. An echocardiogram demonstrated a large pericardial effusion with the swinging heart syndrome. The unexpected finding was the predominant anterior location of the effusion.

Disposition kinetics of quinidine.

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.