Absorption of digoxin from the distal parts of the intestine in man

Ochs, Hermann R.; Bodem, G; Pk, Schäfer; Kodrat, G; Hj, Dengler

doi:10.1007/bf00614003

Cited by 32 publications

(4 citation statements)

References 9 publications

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“…As drug absorption in rats may vary dramatically between the different segments of the gastrointestinal tract (43), the presence of a second peak indicates a reabsorption phase, attributable to a later absorption of digoxin in the distal parts of the intestine. Digoxin is extensively absorbed in the distal part of the bowel (44), and its absorption in rat small intestine is site-dependent and linked to P-gp activity, which varies all along the intestine (increasing from duodenum to ileum) (45). Western blot studies performed in wild, untreated animals confirmed that P-glycoprotein expression increases from proximal to distal small intestine (46).…”

Section: Discussionmentioning

confidence: 85%

Modification of the P-Glycoprotein Dependent Pharmacokinetics of Digoxin in Rats by Human Recombinant Interferon-α

Reguiga¹,

Bonhomme-Faivre²,

Orbach-Arbouys

et al. 2005

Pharm Res

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Section: Discussionmentioning

confidence: 85%

Modification of the P-Glycoprotein Dependent Pharmacokinetics of Digoxin in Rats by Human Recombinant Interferon-α

Reguiga¹,

Bonhomme-Faivre²,

Orbach-Arbouys

et al. 2005

Pharm Res

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“…In contrast, the mRNA expression of Abcb1a (Mdr1) and protein expression of P-gp in the upper small intestine were significantly increased in the elemental diet group, and were also increased, though not significantly, in the semi-digested diet group and digested diet group. Digoxin absorption occurs predominantly at the proximal part of the small intestine, [36][37][38][39][40] so changes of Slco (Oatp) family influx transporter and Abc (Mdr) family efflux transporter expression levels at the upper small intestine are most likely to influence digoxin absorption kinetics.…”

Section: Discussionmentioning

confidence: 99%

Influence of Long-term Enteral Nutrition on Pharmacokinetics of Digoxin in Rats

Higashi

Tanaka

Imanishi

et al. 2013

Drug Metabolism and Pharmacokinetics

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This study was designed to clarify the influence of long-term enteral nutrition (EN) on the pharmacokinetics of digoxin. Rats were fed EN diets (semi-digested, digested, and elemental) for 4 weeks, then digoxin (0.05 mg/kg) was administered orally. The AUC(0-∞) and k(a) of digoxin were significantly reduced in the semi-digested diet group versus the control, while the AUC(0-∞) was significantly increased in the digested and elemental diet groups. The mRNA level of Slco1a4 was significantly reduced at the upper small intestine in all EN groups. Further, the expression levels of P-glycoprotein (P-gp) protein and Abcb1a mRNA were increased at the same site in all EN groups, and the increases were significant in the elemental diet group. Cyp3a2 protein and mRNA expressions were significantly reduced in the liver in the digested and elemental diet groups. Abcb1a mRNA was also significantly reduced in the kidney in these groups. These results indicate that the absorption kinetics at the small intestine is influenced by semi-digested diet, and the elimination kinetics in the liver and kidney are influenced by digested and elemental diet. Semi-digested diet also altered digoxin pharmacokinetics in humans. Thus, the effect of long-term EN on digoxin pharmacokinetics depended on the dietary components.

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“…Digoxin is absorbed primarily from the small intestine. 10,11 As a class, GI promotility agents can potentially decrease the available intestinal absorption time of concomitantly administered drugs, thereby effecting a reduction in total drug bioavailability. 12,13 For example, previous studies have shown that metoclopramide and cisapride reduce the GI absorption of digoxin, 11,14 an agent with a narrow therapeutic window that is commonly prescribed for congestive heart failure.…”

confidence: 99%

The Effects of Tegaserod (HTF 919) on the Pharmacokinetics and Pharmacodynamics of Digoxin in Healthy Subjects

Zhou

Ledford

Hubert

et al. 2001

The Journal of Clinical Pharma

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Tegaserod (HTF 919) is a highly specific 5-HT4 receptor partial agonist that exhibits promotile activity throughout the gastrointestinal tract and is under development for the treatment of functional gastrointestinal motility disorders. The present study was designed to assess the effect of multiple doses of tegaserod on the single-dose pharmacokinetics and pharmacodynamics of digoxin, a commonly prescribed agent for congestive heart failure. The study was an open-label, randomized, two-period crossover design of 12 healthy subjects. One treatment included digoxin treatment alone; the other treatment included a combined digoxin and tegaserod treatment. On day 1 of the digoxin treatment period, subjects received a single 1 mg oral dose of digoxin. In the combined tegaserod/digoxin treatment period, subjects received a single oral dose of 1 mg digoxin after 3 days of tegaserod (6 mg bid). After coadministration of tegaserod, systemic exposure to digoxin was decreased; mean AUC decreased by 11.9% (p < 0.05) relative to digoxin alone. Cmax was decreased by about 15% (p < 0.05). The 0.5-hour difference in the median tmax between the two treatments was not statistically significant. Because the steady-state trough concentration of digoxin (C(SS,min)) correlates with pharmacological effects, C(SS,min) for digoxin alone and in combination with tegaserod was simulated based on both parametric compartmental modeling and nonparametric superpositioning approaches. The predicted arithmetic mean C(SS,min) for combination therapy is 86% to 89% of that following digoxin alone. Likewise, the predicted arithmetic mean steady-state peak concentration (C(SS,min)) and AUC at steady state during a dosing interval (AUC(SS,tau)) have a similar decrease. This extent of decrease in systemic exposure of digoxin at steady state is unlikely to be clinically relevant. Administration of tegaserod (6 mg bid) was well tolerated, both alone and in combination with a single dose of digoxin. There were no pharmacodynamic changes in ventricular rate and QT interval following coadministration of tegaserod with digoxin. The 1.5-hour and 2-hour postdose plasma concentrations of tegaserod on days 3 and 4 confirmed adequate exposure. In conclusion, dose adjustment for digoxin is unlikely to be needed when tegaserod is coadministered.

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Absorption of digoxin from the distal parts of the intestine in man

Cited by 32 publications

References 9 publications

Modification of the P-Glycoprotein Dependent Pharmacokinetics of Digoxin in Rats by Human Recombinant Interferon-α

Modification of the P-Glycoprotein Dependent Pharmacokinetics of Digoxin in Rats by Human Recombinant Interferon-α

Influence of Long-term Enteral Nutrition on Pharmacokinetics of Digoxin in Rats

The Effects of Tegaserod (HTF 919) on the Pharmacokinetics and Pharmacodynamics of Digoxin in Healthy Subjects

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