Effect of quinidine on plasma concentrations of digoxin.

Ejvinsson, G

doi:10.1136/bmj.1.6108.279

Cited by 154 publications

(35 citation statements)

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“…Studies in this hospital pointed out the possibility that a pharmacokinetic drug interaction between quinidine and digoxin may partially explain this side-effect. It was found that the plasma digoxin levels increased when quinidine was added to the therapy (Ejvinsson, 1977(Ejvinsson, , 1978a(Ejvinsson, , 1978b. This finding has been independently confirmed by other investigators (Leahey, Reifell, Drusin, Heissenbuttel, Lovejoy & Bigger, 1978).…”

Section: Introductionmentioning

confidence: 74%

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Effect of quinidine on plasma concentration and renal clearance of digoxin. A clinically important drug interaction.

Dahlqvist¹,

Ejvinsson²,

Schenck‐Gustafsson³

1980

Brit J Clinical Pharma

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1 Thirty patients on maintenance digoxin therapy and admitted for cardioversion of atrial fibrillation were closely monitored with regard to plasma levels of digoxin and quinidine. 2 Seventeen of these patients were kept on maintenance digoxin therapy. After an initial lag period of 6 to 18 h after the addition of quinidine their digoxin levels started to increase and had increased by between 20 and 330% after 3 days on quinidine. Side-effects attributed to the raised digoxin concentration occurred in 6 of these patients. 3 As studied in 5 of these 17 patients the renal clearance of digoxin decreased markedly when quinidine was added to the therapy. There was also a slight but significant reduction in creatinine clearance (n = 4). 4 In 13 patients digoxin was discontinued 36 h prior to the first quinidine dose. Also in these patients digoxin plasma levels increased significantly. 5 It is concluded that quinidine causes an unpredictably large increase in plasma digoxin and that this effect is probably at least initially to a large part due to a redistribution of digoxin in the body. The relative contributions of re-distribution and impaired renal clearance of digoxin to the increase in digoxin steady-state levels are presently unknown. 6 It is recommended that close monitoring of digoxin concentration and appropriate reduction of the maintenance dose is undertaken when quinidine is to be given to patients on digitalis therapy.

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Section: Introductionmentioning

confidence: 74%

“…Data from 12 of these patients have been published in preliminary reports (Ejvinsson, 1977(Ejvinsson, , 1978b. In two of the patients quinidine treatment had to be discontinued after 12 h due to ventricular tachycardia and/or ventricular fibrillation.…”

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confidence: 99%

Effect of quinidine on plasma concentration and renal clearance of digoxin. A clinically important drug interaction.

Dahlqvist¹,

Ejvinsson²,

Schenck‐Gustafsson³

1980

Brit J Clinical Pharma

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“…This decrease in the affinity of the receptor for digoxin under nonsaturating conditions should increase serum digoxin concentration as long as quinidine is present. Although the extent to which in vivo bound digoxin levels would decrease is unclear, it should be pointed out that, because <1% of the total body glycoside stores are present in the serum of digoxin-treated patients (44), a loss of 1% of tissue digoxin stores could result in a twofold increase in serum digoxin concentration, and would approximate the increase frequently noted clinically following quinidine administration (1,2,4,7,8,(11)(12)(13)(14)(15). The precision of our experiments on purified Na,K-ATPase (Table V) and in a previous study (32), is significantly slower than its dissociation rate from receptors in skeletal and cardiac muscle (45), tissues containing the major pools of glycoside binding sites in man (44).…”

Section: Resultsmentioning

confidence: 99%

Effect of quinidine on the digoxin receptor in vitro.

Ball¹,

Tse-Eng²,

Wallick³

et al. 1981

J. Clin. Invest.

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A B S T R A C T To investigate the basis for a clinically important digitalis-quinidine interaction that is characterized by increases in serum digoxin concentrations when quinidine is administered to digoxin-treated patients, we have studied in vitro the interaction of quinidine with the digoxin receptor. Evidence has been obtained that quinidine is capable of decreasing the affinity for digoxin of cardiac glycoside receptor sites on purified Na,K-ATPase and on intact human erythrocyte membranes. As others have shown, quinidine is capable of inhibiting Na,K-ATPase activity, and evidence has been obtained in the current study that, while quinidine can reduce the affinity of the enzyme for digoxin, it is also capable of acting together with digoxin in inhibiting enzyme activity to a degree greater than the inhibitory effect of digoxin alone. The concentrations of digoxin and quinidine used in this study were considerably greater than their therapeutic serum concentrations. Nevertheless, these observations are consistent with the hypothesis that the increases in serum digoxin concentrations and the decreases in volumes of digoxin distribution observed clinically when quinidine is administered to digoxintreated patients may reflect, at least in part, a decrease in the affinity of tissue receptors for digoxin. The possibility must also be considered that enhanced cardiac effects of digoxin may occur clinically as the result of an augmentation, by quinidine, of digoxin effects, which more than compensates for the modest reduction in digoxin binding.

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“…Since the unexpected discovery that quinidine causes a marked increase in the steady-state plasma concentration of digoxin (Ejvinsson, 1977;Kaufman 1978;Ejvinsson 1978;Leahey, Reiffel, Drusin, Heissenbuttel, Lovejoy & Bigger, 1978;Doering & Konig, 1978) work has progressed to clarify the underlying mechanisms. It was shown that quinidine also exerts this effect in patients where digoxin maintenance therapy was discontinued 2 days before quinidine treatment suggesting redistribution as a mechanism (Leahey et al, 1978;Dahlqvist, Ejvinsson & Schenck-Gustafsson, 1980).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of digoxin in patients subjected to the quinidine‐ digoxin interaction.

Schenck‐Gustafsson¹,

Dahlqvist²

1981

Brit J Clinical Pharma

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1 This study was designed to evaluate pharmacokinetically the digoxin‐ quinidine interaction in patients with atrial fibrillation. 2 Five patients on maintenance digoxin therapy were given [3H]‐digoxin as a single i.v. dose before and during quinidine therapy and the elimination of [3H]‐digoxin from plasma and excretion in urine were determined. 3 The mean steady state plasma concentration of digoxin increased from 0.7 to 1.3 nmol/l after quinidine administration. 4 The apparent volume of distribution of digoxin decreased on the average 38%. Renal clearance and the total body clearance of digoxin decreased 51 and 56% respectively (mean values). Also non renal clearance was reduced. The fraction of digoxin excreted unmetabolised in urine did not change during quinidine treatment. The mean elimination half life of digoxin increased from 49 to 72 h during quinidine. 5 In two patients the DC‐shock did not cause a conversion to sinus rhythm. However, the quinidine induced changes in the pharmacokinetics of digoxin in these patients did not differ from the others. 6 Quinidine appears to decrease the amount of digoxin distributed to body tissue(s). In addition, the reduction of renal clearance of digoxin and the observed unchanged clearance of creatinine suggests an inhibition of the renal secretion of digoxin.

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Effect of quinidine on plasma concentrations of digoxin.

Cited by 154 publications

References 1 publication

Effect of quinidine on plasma concentration and renal clearance of digoxin. A clinically important drug interaction.

Effect of quinidine on plasma concentration and renal clearance of digoxin. A clinically important drug interaction.

Effect of quinidine on the digoxin receptor in vitro.

Pharmacokinetics of digoxin in patients subjected to the quinidine‐ digoxin interaction.

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