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

Schäfer, S. G.; Schuhmann, G.; Doering, W.; Fichtl, B.

doi:10.1016/s0009-2797(85)80128-9

Cited by 9 publications

(3 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SI Table S6 lists selected drugs that have been investigated for IE, mostly in the context of drug absorption. , Many studies have provided evidence to support regional IE through the use of Ussing chambers, everted intestinal sacs, perfused intestinal segments, and in vivo with AC treatment. ,,,,− Several drugs were discovered to undergo extensive intestinal excretion only after investigation using various in vitro and in vivo models, and limited examples have unambiguously demonstrated fecal elimination resulting from regional IE. ,, The studies with apixaban provide an integrated data set that demonstrated direct IE that is responsible for 20–50% of the systemic clearance in humans and animal species.…”

Section: Intestinal Excretion Is One Of the Fundamental Mechanisms Fo...mentioning

confidence: 99%

Intestinal Excretion, Intestinal Recirculation, and Renal Tubule Reabsorption Are Underappreciated Mechanisms That Drive the Distribution and Pharmacokinetic Behavior of Small Molecule Drugs

Zhang¹,

Wei

Hop³

et al. 2021

J. Med. Chem.

View full text Add to dashboard Cite

Drug reabsorption following biliary excretion is well-known as enterohepatic recirculation (EHR). Renal tubular reabsorption (RTR) following renal excretion is also common but not easily assessed. Intestinal excretion (IE) and enteroenteric recirculation (EER) have not been recognized as common disposition mechanisms for metabolically stable and permeable drugs. IE and intestinal reabsorption (IR:EHR/EER), as well as RTR, are governed by dug concentration gradients, passive diffusion, active transport, and metabolism, and together they markedly impact disposition and pharmacokinetics (PK) of small molecule drugs. Disruption of IE, IR, or RTR through applications of active charcoal (AC), transporter knockout (KO), and transporter inhibitors can lead to changes in PK parameters. The impacts of intestinal and renal reabsorption on PK are under-appreciated. Although IE and EER/RTR can be an intrinsic drug property, there is no apparent strategy to optimize compounds based on this property. This review seeks to improve understanding and applications of IE, IR, and RTR mechanisms.

show abstract

Section: Intestinal Excretion Is One Of the Fundamental Mechanisms Fo...mentioning

confidence: 99%

Intestinal Excretion, Intestinal Recirculation, and Renal Tubule Reabsorption Are Underappreciated Mechanisms That Drive the Distribution and Pharmacokinetic Behavior of Small Molecule Drugs

Zhang¹,

Wei

Hop³

et al. 2021

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…In vivo studies in guineapigs found that the jejunum and the colon had similar digitoxin secretory capacity, while digoxin excretion was higher in the jejunum (Schafer et al 1985). The question of which intestinal site has maximal digitalis glycoside secretory capacity is controversial.…”

Section: Eliminationmentioning

confidence: 99%

Digitalis

Mooradian

1988

Clinical Pharmacokinetics

View full text Add to dashboard Cite

The intestinal absorption of digoxin is essentially a passive non-saturable diffusion process, although a saturable carrier-mediated component also plays an important role. The bioavailability varies between 40 and 100%: the presence of food may reduce the peak serum concentration, but does not reduce the amount of digoxin absorbed. Recent development of a capsule containing a hydroalcoholic vehicle may reduce interindividual variations in absorption. Pharmacokinetic analysis of the distribution of digoxin suggests 3 compartments, the slow distribution phase accounting for the lag time between the inotropic effects and the plasma concentration profile. Digoxin is extensively bound to tissues such as myocardium, renal, skeletal muscle as well as red blood cells, but not to adipose tissue. Plasma protein binding varies between 20 and 30%: displacement of digoxin from protein binding sites does not cause significant clinical effects. As expected, haemodialysis or exchange transfusions do not significantly alter the body load of digoxin. The apparent volume of distribution of digoxin varies between 5 and 7.3 L/kg; this may be reduced by, for example, electrolyte abnormalities which reduce digoxin binding to the myocardium. The elimination half-life of digoxin is 36 hours, with 60 to 80% being excreted unchanged, by passive glomerular filtration and active tubular secretion. The remainder is excreted non-renally. Clearance is therefore dependent on renal function and declines in renal disease and in elderly patients. Digoxin interacts with other drugs at any stage of absorption (e.g. cholestyramine), distribution (e.g. quinidine), metabolism (e.g. phenytoin) or elimination (e.g. diltiazem). Patients should, therefore, be carefully monitored when changing a therapeutic regimen which includes any drugs known to interact with digoxin. Clinical monitoring is more important than therapeutic drug monitoring which should be reserved for suspected toxicity, doubts about efficacy, or in cases of poor compliance. With the advent of newer treatment modalities, digoxin is no longer the treatment of first choice in supraventricular arrhythmias and congestive heart failure. However, with careful monitoring, digoxin remains an important therapeutic option.

show abstract

“…By contrast a dose-dependence of the nifedipine/digoxin interaction could not be shown [11]. A reduction in renal and non-renal clearance of digoxin is considered to be the source of the calcium antagonist-digoxin interference [12,13]. The increased digoxin plasma levels caused by concurrent administration of a calcium channel blocker are pharmacodynamically relevant, meaning that there is evidence for an enhanced positive inotropic effect due to the elevated digoxin concentrations [1].…”

Section: Introductionmentioning

confidence: 99%

The interaction of the calcium antagonist RO 40‐5967 with digoxin.

Siepmann

Kleinbloesem

Kirch

1995

Brit J Clinical Pharma

View full text Add to dashboard Cite

1. The interaction of the newer calcium antagonist Ro 40‐5967 with digoxin was investigated in 42 healthy subjects under steady state conditions. 2. After an adequate loading dose digoxin 0.375 mg once daily was given alone for 1 week. Afterwards three different doses (50, 100, 150 mg daily) of the calcium antagonist Ro 40‐5967 were administered to three groups of 14 subjects each for 1 week concurrently with digoxin 0.375 mg daily. 3. Ro 40‐5967 led to an increase of mean maximum digoxin plasma concentrations (Cmax) and AUC. For AUC this effect was significantly dose‐dependent. 4. Increasing doses of the calcium antagonist led to a stepwise rise of the PQ‐time in ECG. 5. A slight fall of heart rate was seen after a 7 day treatment of digoxin alone. This effect was more pronounced when Ro 40‐5967 was added to the medication. No significant changes of stroke volume and blood pressure were noted. 6. In conclusion Ro 40‐5967 led to a significant elevation of the plasma concentration‐time curve (AUC) of digoxin. This effect was dose‐dependent.

show abstract

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

Cited by 9 publications

References 12 publications

Intestinal Excretion, Intestinal Recirculation, and Renal Tubule Reabsorption Are Underappreciated Mechanisms That Drive the Distribution and Pharmacokinetic Behavior of Small Molecule Drugs

Intestinal Excretion, Intestinal Recirculation, and Renal Tubule Reabsorption Are Underappreciated Mechanisms That Drive the Distribution and Pharmacokinetic Behavior of Small Molecule Drugs

Digitalis

The interaction of the calcium antagonist RO 40‐5967 with digoxin.

Contact Info

Product

Resources

About