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Biomedical subjects

W Doering

Publications and source records attributed to W Doering.

At least 37 records · Page 2Linked to original sources
PubMed1987

Pharmacokinetic interaction study with ramipril and digoxin in healthy volunteers.

Coadministration of captopril has been shown to increase serum digoxin concentration. The effects of ramipril, a new angiotensin converting enzyme inhibitor, on serum digoxin concentration after multiple dosing were studied in 12 healthy volunteers. All subjects were receiving steady-state digoxin medication (0.5 mg daily), and ramipril (5 mg daily) was coadministered for 14 days. Serum digoxin concentration was measured repeatedly before, during and up to 1 week after ramipril coadministration at 8 a.m. (trough values) and on selected trial days at 11 a.m., 3 hours after the morning medication. Simultaneously, blood levels of ramipril and its active metabolite diacid were determined. Volunteers were followed closely for side effects and for changes in blood pressure, heart rate and electrocardiogram. Safety pharmacology included serial determination of sodium, potassium, serum glutamic oxaloacetic transaminase, creatinine and a full blood count. Mean serum digoxin concentration was not significantly influenced by ramipril coadministration with trough levels of 0.90 +/- 0.24 before, 0.93 +/- 0.38 during and 0.82 +/- 0.33 ng/ml after ramipril medication. The increase in serum digoxin concentration 3 hours after the morning dose was also not significantly affected by ramipril. Serum levels of ramipril and its diacid showed a wide range of variation. Mean serum potassium increased by 0.3 mmol/liter during ramipril coadministration with development of symptomless hyperkalemia (6.0 mmol/liter) in 1 subject. The only other side effect possibly related to ramipril was a dry cough in 1 subject. Both drugs were well tolerated. Ramipril showed no significant influence on serum digoxin levels in healthy volunteers.

Adult↗
PubMed1985

Influence of quinidine on the intestinal secretion of digoxin and digitoxin in guinea pigs.

The secretion of digoxin and digitoxin into in situ perfused jejunal and colonic segments of normal or quinidine treated guinea pigs was studied. Quinidine was administered intravenously by constant rate infusion resulting in a quinidine plasma concentration of about 6 micrograms/ml. After 2 h digoxin or digitoxin was injected i.v. (10 micrograms/kg). The quinidine treatment enhanced the plasma concentration of [3H]digoxin to about 140% as compared to controls, whereas the [3H]digitoxin concentration was not influenced by the quinidine infusion. Both, digoxin and digitoxin were secreted against a concentration gradient into the intestinal lumen. During the experimental period of 180 min controls secreted 0.24% of the administered digoxin dose per cm of jejunal and 0.13% per cm of colonic segment. Quinidine treatment resulted in a decrease of the jejunal digoxin secretion to about 80% of the control values. In both, jejunum and colon the concentration ratio between lumen and plasma (L/P) was diminished by quinidine to 50% as compared with the controls. The amount of [3H]digitoxin secreted into the intestinal segments was decreased by quinidine from 0.19% of the dose/cm to 0.13% in the jejunal and from 0.17% to 0.12% in the colonic segments, respectively. The decrease of the L/P ratio for [3H]digitoxin was more pronounced in the colon (58%) than in the jejunum (77% of the control values). As compared with controls the content of [3H]digoxin in the jejunal as well as colonic tissue was decreased by quinidine to 60% or 73%, respectively. On the other hand quinidine increased the tissue content of [3H]digitoxin in jejunum (+56%) and colon (+88%). In conclusion quinidine inhibits the intestinal secretion of both, digoxin and digitoxin, possibly by different mechanisms.

Animals↗
PubMed1983

Effect of coadministration of verapamil and quinidine on serum digoxin concentration.

Both quinidine and verapamil are known to increase the serum digoxin concentration (SDC), and other calcium channel blockers may have a similar effect. Since an increasing number of patients is likely to be treated concurrently with digoxin, quinidine and a calcium channel blocker, a study was done to show whether coadministered quinidine and verapamil would cooperate to elevate the SDC. Nine healthy volunteers on basic digoxin treatment (Leanoxin 0.125 mg t.i.d.) were treated with placebo, verapamil 80 mg t.i.d. and the combination (verapamil 80 mg plus quinidine base 160 mg t.i.d.), for 2 weeks in a randomized sequence. Drug concentration and various cardiovascular parameters were measured each week and/or at the end of each treatment period. Steady state concentrations were always obtained within 1 week and drug levels at the end of the first and second weeks of treatment were almost identical. The plasma verapamil concentration (PVC) was 25.8 +/- 9.9 ng/ml during coadministration of verapamil and digoxin, and 15.7 +/- 6.9 ng/ml during combined verapamil-quinidine coadministration, when the serum quinidine concentration (SQC) was 1.26 +/- 0.50 micrograms/ml. Compared to placebo SDC rose by 53% from 0.62 +/- 0.16 to 0.95 +/- 0.29 ng/ml (p less than 0.001) during verapamil treatment and further to 1.58 +/- 0.38 ng/ml (155% rise; p less than 0.001) during combined verapamil-quinidine coadministration. Thus each drug maintained its own effect on SDC in the presence of the other, and their actions became combined in increasing the SDC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Interaction between digoxin and calcium antagonists and antiarrhythmic drugs.

The influence of several calcium antagonists and antiarrhythmic drugs on digoxin kinetics and actions were investigated in 36 healthy men during digoxin steady state (0.375 mg/day). The subjects were randomly assigned to three subgroups and each group received placebo (control) and two of the following regimens (doses three times a day) in a randomized sequence for 2 wk each: verapamil (80 mg) and nifedipine (10 mg), verapamil (120 mg) and gallopamil (50 mg), or propafenone (150 mg) and quinidine (250 mg). Plasma digoxin concentration (PDC) rose during the cotreatments in the sequence: gallopamil (+16%) less than propafenone (+37%) less than nifedipine (+45%) less than verapamil (almost independent of dose, +69%) less than quinidine (+118%). These increases in PDC correlated closely to decreases in renal digoxin clearances. Renal creatinine clearance was virtually unaffected. The rise of PDC resulted in increased glycoside effects, as measured by the shortening of systolic time intervals and flattening of T wave. There was a linear correlation between PDC and changes in mean corrected electromechanical systole and T wave flattening. We conclude that, in addition to quinidine, other antiarrhythmic drugs and various calcium antagonists interact kinetically with digoxin and that the increasing PDCs are cardioactive.

Adult↗
PubMed1983

[Effect of tiaprofenic acid on serum digoxin concentration].

The effect of concomitant tiaprofenic acid (Surgam) administration (200 mg t.i.d.) on serum digoxin concentration (SDC) was evaluated in 12 healthy volunteers on digoxin maintenance treatment. During a 10-day coadministration period with tiaprofenic acid no significant increase in SDC was observed (0.97 +/- 0.24 vs. 1.12 +/- 0.21 ng/ml, p less than 0.05). Mean tiaprofenic acid concentration amounted to 2.85 +/- 1.94 micrograms/ml 14 h after last drug intake. The incidence of adverse reactions was minimal with gastrointestinal upset in one person. Tiaprofenic acid had no influence on red or white blood cell count. Thus, in contrast to various other nonsteroidal antiinflammatory drugs coadministration of tiaprofenic acid (600 mg daily) has no relevant influence on serum digoxin levels.

Adult↗
PubMed1983

The quinidine-digoxin interaction in patients with impaired renal function.

Quinidine has been reported to reduce clearance and the distribution volume of digoxin. Data are presented indicating that serum digoxin concentration (SDC) is increased throughout the coadministration of quinidine. This strongly suggests that the quinidine-induced reduction of digoxin clearance is the main mechanism underlying this drug interaction. It has been suggested that beside renal clearance quinidine also reduces non-renal clearance of digoxin. Direct evidence is provided by a study in patients with impaired renal function. Irrespective of the degree of renal impairment, quinidine increases SDC to about the same amount as found in patients with normal renal function. Since quinidine does not interfere with plasma protein binding of digoxin, this implies a decrease in non-renal clearance. In all patient groups the incidence of this drug interaction is rather high; however, pronounced interindividual differences occur as regards the extent of the increase in SDC. Regardless of the state of renal function careful monitoring of digitalized patients is mandatory once quinidine therapy is initiated. Since it may take a week or more until a new steady state is established in patients with impaired renal function, this period of close monitoring should be extended correspondingly.

Blood Proteins↗
PubMed1982

Quinidine-digoxin interaction: evidence for involvement of an extrarenal mechanism.

The influence of quinidine 750mg per day for one week on serum digoxin concentration (SDC) was evaluated in digitalized anuric patients on chronic haemodialysis. During quinidine administration the SDC increased markedly, from 0.84 +/- 0.37 to 1.58 +/- 0.72 ng/ml (p less than 0.01), a comparable effect ot that reported previously in patients with normal renal function. Neither in vitro nor in vivo did quinidine alter the serum protein binding of digoxin. The increase in SDC in anuric patients indicates a decrease in the extrarenal clearance of digoxin, which means that mechanisms other than of renal origin are also involved in the interaction of quinidine and digoxin. There was great interindividual variability in the extent of the quinidine-induced rise in SDC. Regardless of the state of renal function, careful monitoring of digitalized patients seems mandatory once quinidine treatment is initiated.

Anuria↗
PubMed1982

Quinidine-digoxin interaction: cardiac efficacy of elevated serum digoxin concentration.

Cardioactivity due to elevated serum digoxin concentration (SDC) after quinidine (Q) and digoxin (D) was evaluated in six healthy subjects by means of measurement of systolic time intervals (STIs). Each subject randomly received basic treatments with 0.2 mg D and placebo (PL1). Randomized coadministrations with Q (1 gm/day), sparteine (SP) (0.8 gm/day), and placebo (PL2) were given for 7-day periods. A steady-state dose of 0.4 mg D was added. Mean SDC increased from 0.48 ng/ml during 0.2 mg D + PL2 to 1.13 ng/ml on 0.2 mg D + Q (P less than 0.05); it was unchanged by SP. On 0.4 mg D there were further shortenings of STIs compared to those on 0.2 mg D + PL2. Q markedly prolonged STIs; the SP effects were similar but less pronounced. When given with Q or SP, the effect of D was obscured by opposing inotropic properties; consequently, despite increasing SDC, measureable STIs were unchanged. The true glycoside effect was determined by comparing the effects of the pure antiarrhythmic to those of the antiarrhythmic with D. These calculations showed that the glycoside effect of the elevated SDC during Q + D dosing was much the same as the effect of 0.4 mg D.

Adult↗
PubMed1982

Effects of i.v. prenalterol in patients with severe cardiac failure at rest and during exercise.

Prenalterol administration (150 micrograms/kg i.v.) exerted beneficial effects on resting and/or exercise cardiac performance in patients with congestive cardiomyopathy (n = 12) and 1 patient with hypertensive heart disease (= group I, n = 13), while the haemodynamic response in patients with severe coronary heart disease (n=3) or cor pulmonale (n = 1) was non-uniform. At rest mean right and left ventricular filling pressures decreased by 26 and 19% (p less than 0.02 and p less than 0.02), respectively, while stroke volume increased by 8% (p less than 0.05), cardiac index by 25% (p less than 0.01) and heart rate by 15% (p less than 0.005) 5 min after prenalterol administration in group I. During exercise there was no further increase in heart rate, while filling pressures decreased and cardiac index increased significantly compared to control exercise. This typical inotropic response to prenalterol was observed in fully digitalised patients. Maximal effects occurred about 15 min after i.v. administration.

Adrenergic beta-Agonists↗
PubMed1981

[Quinidine-digoxin interaction (author's transl)].

An additional dose of 500 mg of rapidly absorbed quinidine increased the digoxin concentration in serum after 3-5 hours by up to 46% and prolonged digoxin half life from 50 to 100 hours in six probands who were on chronic quinidine-digoxin medication. These effects were not elicited regularly in persons pretreated with digoxin only. The results show that quinidine both diminishes elimination and produces transient redistribution of digoxin. Chronic quinidine medication leads to protracted digoxin elimination resulting in marked prolongation of digoxin half life. This is the reason for persisting increase of digoxin concentration in serum. Estimation of serum digoxin levels should thus be done 8 hours after the last quinidine (and digoxin) medication at the earliest. On cessation of digoxin, as is done preparing for electric cardioversion, one should remember that digoxin elimination is clearly prolonged should quinidine treatment be continued.

Digoxin↗
PubMed1981

Quinidine-digoxin interaction: effect of quinidine on 86Rb-uptake of human erythrocytes.

Co-administration of quinidine results in a marked increase in serum digoxin concentration (SDC). The implication of this increase in SDC in regard to an increased digoxin effect on the heart is controversial. The 86Rb-erythrocyte-assay represents a perfect model to study whether quinidine interferes with digoxin at the Na-K-ATPase (the so called glycoside receptor) and thus presumably with the inotropic effect of the glycoside. The inhibitory effect of digoxin (0-150 ng/ml) on the 86Rb-uptake was measured in the absence and presence of quinidine in therapeutic or higher concentrations (0-60 microgram/ml). Addition of quinidine produced no effect on digoxin-induced inhibition of Na-K-ATPase activity. Together with our clinical observations these results strongly suggest that the increased SDC during concomitant quinidine therapy actually reflects an increased digoxin effect on the heart.

Digoxin↗
PubMed1979

Quinidine-digoxin interaction: Pharmacokinetics, underlying mechanism and clinical implications.

Administration of quinidine with digoxin increased serum digoxin concentrations in 79 patients and five volunteers. In 38 patients on a constant glycoside maintenance dose, the addition of quinidine to digoxin therapy resulted in a mean 2.5-fold increase (from 0.98 +/- 0.37 to 2.47 +/- 0.71 ng per milliliter, mean +/- 1 S.D.) (P less than 0.001). The addition of quinidine decreased renal glycoside clearance (from 91.6 +/- 27.8 to 40.6 +/- 15.8 ml per minute) (P less than 0.001). Unlike other investigations, our studies provided no evidence that quinidine displaced digoxin at specific cardiac binding sites. The elevated digoxin levels found during quinidine administration suggest a 30 to 50 per cent reduction of the digoxin dose. Adverse reactions to combined quinidine-digoxin therapy may be partly due to digitalis intoxication.

Adult↗
PubMed1978

[A questionnaire for early recognition of digitalis intoxication (author's transl)].

The diagnostically relevant data of 1164 patients under digitalis were stored in a computer and compared statistically for toxic and nontoxic patients. Resulting from this a questionnaire was developed in which each item was weighted according to its own diagnostic value. In a prospective study 77 suspected cases of digitalis intoxication were classified according to their scoring in the questionnaire. In 92% of the patients this classification was confirmed by the final diagnosis (after withdrawal of the glycoside). Mean score and mean serum digoxin concentration (SDC) of the toxic patients were significantly higher. There was a high consensus between the final diagnosis, the classification by the questionnaire and the SDC. The questionnaire proved to be a useful aid in the bedside diagnosis of digitalis intoxication.

Arrhythmias, Cardiac↗