Talinolol Digoxin

Several in vitro studies with different probes (talinolol, digoxin, and vinblastine) also confirm the findings that GFJ inhibits the efflux of P-gp substrates (20,54,73). 

P-gp (ABCB1) Verapamil, digoxin, mitoxantrone, vinblastine, doxorubicin, losartan, talinolol, cortisol, dexamethasone, colchicine, loperamide, domperidone, indinavir, erythromycin, tetracycline, itraconazole, cyclosporine, methotrexate, amitryptyline, phenobarbital, morphine, cimetidine, and others... 

K Westphal, A Weinbrenner, T Giessmann, M Stuhr, G Franke, M Zschiesche, R Oertel, B Terhaag, HK Kroemer, W Siegmund. Oral bioavailability of digoxin is enhanced by talinolol evidence for involvement of intestinal p-glycoprotein. Clin Pharmacol Ther 68 6-12, 2000. 

Despite our inability to predict quantitatively the influence P-gp may have on the in vivo transport of substrates in normal tissues with respect to other processes, in vitro experiments remain the best means of demonstrating that a compound is a substrate for polarized efflux. Nearly all experiments designed to study the extent of P-gp efflux of test compounds in vivo require adequate in vitro data to support the hypothesis (48,217,226,454). In vitro studies on P-gp substrates such as vinblastine, paclitaxel, cyclosporin A, talinolol, acebutolol, and digoxin have provided a good indication of the effect of P-gp on the in vivo pharmacokinetic behavior of these compounds. These studies show that results from the in vitro studies provide a qualitative estimate of the influence of P-gp on its in vivo pharmacokinetic behavior. Findings such as these give confidence that results from in vitro experiments can be extrapolated to explain modulation of dmg disposition by P-gp efflux. 

In conclusion, direct evidence of transporter-mediated drug interaction can be obtained relatively readily if a transporter substrate, such as digoxin or talinolol, undergoes minimal metabolism. In addition, transporter-mediated drug interactions can also be readily defined if potent and specific transporter inhibitors (or inducers), such as PSC833 and GF120918, are available. 

Inhibitors listed for P-gp are those that showed >25 % increase in digoxin/fexofenadine/talinolol AUC. UTD UpToDate (http //www.uptodate.com/contents/search)... 

Lipophilic, amphiphilic with weak organic cation, containing hydrogen bond donor and acceptor, such as digoxin, talinolol, vinblastine, paclitaxel, fexofenadine, quinidine, loperamide, topotecan, gleevec, colchicines,... 

In general there appears to be no pharmacokinetic interaction between digoxin and beta biockers, although talinolol and carvedilol appear to increase the bioavailability of digoxin. Pharmacodynamic interactions, resulting in additive bradycardia, are possible. A few cases of excessive bradycardia have been reported when propranolol was used to control digitalis-induced arrh i h-mias. 

Talinolol. In healthy subjects talinolol 100 mg orally substantially increased the bioavailability of a single 500-microgram dose of digoxin. The AUCq 72 and the maximum serum levels of digoxin were increased by 23% and 45%, respectively. Conversely, intravenous talinolol 30 mg had no effect on digoxin pharmacokinetics. ... 

It has also been suggested that the interaction between digoxin and talinolol may be dosage form dependent. More study is needed. 

Concurrent use appears, on the whole, beneficial, but the potential for additive bradycardia should be borne in mind. Use of beta blockers in cases of digoxin toxicity should be undertaken with great care. In addition, it may be prudent to monitor digoxin levels with talinolol, and also with carvedilol, particularly in children. It has been suggested that the dose of digoxin should be reduced by at least 25% in children given carvedilol, with further adjustments as required. ... 

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