Studies of quinidine plasma levels and rate of decline following cessation of quinidine administration

Swisher, William P.; Wedell, Harold G.; Cheng, John T.O.; Sutton, George C.; Sutton, Don C.

doi:10.1016/0002-8703(54)90302-6

Cited by 21 publications

(4 citation statements)

References 7 publications

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“…The effect of cardiac failure on drug plasma concentration has been reported in a number of publications (3)(4)(5)(6)(7)(8)(9)(10)(11). These clinical studies dealing with quinidine, lidocaine and procainamide show that patients with heart failure have higher drug plasma concentrations and often, lower rate of drug elimination than healthy volunteers.…”

Section: Resultsmentioning

confidence: 99%

“…Congestive heart failure is a clinical condition which has been described as affecting drug disposition: administration of lidocaine, quinidine, procainamide in patients with heart failure was found to be associated with higher drug plasma concentrations and more frequent manifestations of toxicity than in control patients (3)(4)(5)(6)(7)(8)(9)(10)(11). Many hypotheses were put forward to explain these last observations, but none could be verified because of the noninvasive techniques used in human experimentations.…”

Section: Introductionmentioning

confidence: 99%

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Disposition kinetics of barbital in hamsters with hereditary heart failure

Beaudoin-Jacob

Marchand

1977

European Journal of Drug Metabolism and Pharmacokinetics

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Within a few minutes after oral administration of sodium barbital, 100 mg/kg, in hamsters with hereditary heart failure, the concentration of the drug was found to be lower in the plasma, kidney, brain and striated muscle of these animals than in the tissue of control hamsters. This could be explained by delayed intestinal absorption, as evidenced by greater amounts of drug recovered from the intestine of cardiomyopathic animals a few minutes after barbital administration. However, 6-24 hours later, the concentration of the drug in these tissues was higher than in those of control hamsters; also, the elimination rate of the drug from these tissues was found to be slower than in control animals. This slower elimination rate of the drug from the tissue of animals in heart failure was responsible for the greater drug bioavailability in the tissues, as reflected by the area under the curve of drug concentration in the tissue vs, time. From in vitro studies of aniline and aminopyrine metabolism by liver microsomal enzymes of hamsters in heart failure, it is concluded that impairment of drug metabolism by the liver may be partially responsible for the slower drug elimination from the body of patients in heart failure.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Disposition kinetics of barbital in hamsters with hereditary heart failure

Beaudoin-Jacob

Marchand

1977

European Journal of Drug Metabolism and Pharmacokinetics

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“…Il nous paraît intéressant de rapprocher nos résultats expéri mentaux de données recueillies en clinique humaine sur les varia tions du taux plasmatique de quinidine au cours de divers états pathologiques [1, 2,6]. Elles indiquent que la vitesse de décrois sance de ce taux est d'autant plus faible que la fibre myocardique est altérée par une hypertrophie ou une insuffisance ventriculaire chez l'Homme.…”

Section: Discussionunclassified

Evolution sanguine et tissulaire des taux de quinidine après une injection veineuse

Armand¹,

Evreux²,

Badinand³

et al. 1969

Pharmacology

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“…It has been known for many years that, after the administration of equivalent doses, plasma quinidine concentrations are generally higher in patients with congestive heart failure than in control patients. 2, 5, 6, 9, 13 Several groups of investigators 2 , 5, 13 have suggested that the elevated quinidine concentrations in these patients were due to a slower rate of drug elimination from the plasma. Kessler and associates,10 on the other hand, reported that the elimination half-life (t!)…”

mentioning

confidence: 99%

Quinidine kinetics in congestive heart failure

Ueda

Dzindzio

1978

Clin Pharma and Therapeutics

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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.

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Studies of quinidine plasma levels and rate of decline following cessation of quinidine administration

Cited by 21 publications

References 7 publications

Disposition kinetics of barbital in hamsters with hereditary heart failure

Disposition kinetics of barbital in hamsters with hereditary heart failure

Evolution sanguine et tissulaire des taux de quinidine après une injection veineuse

Quinidine kinetics in congestive heart failure

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