Talinolol

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... 

C7H11NO 3/73-53-3) see Acetohexamide Glibenclamide Glipizide Gliquidone Lomustine Talinolol cyclohexylmagnesiiun bromide... 

C13H20N2O4 133228-95-2) see Talinolol 4-(p-nitrophenoxy)-3-methyl-2-buten-l-ol (C11H13NO4 171180-10-2) see Troglitazone 4-(p-nitrophenoxy)-3-methyl-2-butenyl acetate (C13H15NO5 171180-09-9) see Troglitazone... 

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. 

Schwarz, U. I., Gramatte, T., Krapp-weis, J., Berndt, A., Oertel, R., von Richter, O., Kirch, W., Unexpected effect of verapamil on oral bioavailability of the beta-blocker talinolol in humans, Clin. Pharmacol. Ther. 1999, 65, 283-290. 

Gramatte, T., Oertel, R., Intestinal secretion of intravenous talinolol is inhibited by luminal R-verapamil,... 

H., Mutschler, E., Terhaag, B., Rosch, W., Langguth, P., Evidence for intestinal secretion as an additional clearance pathway of Talinolol enantiomers concentration and dose dependent absorption in vitro and in vivo, Pharm. Res. 1996, 13, 514-522. 

An SPE cartridge can be used multiple times, especially after the samples are pretreated with protein precipitation. Bourgogne et al. (2005) quantitated talinolol, a p -adrenoceptor antagonist used to treat arterial hypertension and coronary heart disease, in human plasma. The sample was first precipitated with perchloric acid and the supernatant was injected directly. An Xterra MS analytical column (50 x 4.6 mm, 3.5 [m, Waters) with a C18 recolumn filter (4x2 mm, 3.5 /.mi, Phenomenex) and a C8 EC cartridge were chosen. The cycle time was 4.8 min and linear range was 2.5 to 200 ng/mL. Protein precipitation allowed the SPE cartridge to be used for more than 90 injections. 

Bourgogne E., Grivet C., and Hopfgartner G., 2005. Determination of talinolol in human plasma using automated online solid phase extraction combined with atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatogr B 820 103. 

Kauffinann, H.M., Schrenk, D., Terhaag, B., Kroemer, H.K. and Siegmund, W. (2000) Induction of P-glycoprotein by rifampin increases intestinal secretion of talinolol in human beings a new type of... 

Rege and colleagues have studied the effect of nonionic surfactants (e.g., Cremophor EL, Tween 80, and TPGS) on membrane transporters [116], Similar results for vitamin E TPGS using talinolol and rhodamine 123 as P-gp substrates have been reported by Bogman et al. ([32] and Collnot and coworkers [40], respectively. 

Deferme S, Mols R, Van Driessche W, Augustijns P (2002b) Apricot extract inhibits the P-gp mediated efflux of talinolol. J Pharm Sci 91 2539-2548. 

P-glycoprotein and surfactants Effect on intestinal talinolol absorption. Clin Pharmacol Ther 77 24-32... 

FIGURE 5 Chiral CEC-ESI/MS analysis of eight /l-blockers 1,1 = oxprenolol, 2,2 = alprenolol, 3,3 = pindolol, 4,4 = metoprolol, 5,5 = propranolol, 6,6 = talinolol, 7,7 = atenolol, 8,8 = carteolol. Reprinted from reference 288 with permission from Wiley-VCH Verlag GmbH. 

Fig. 3.8 Structures of propranolol (1), betaxolol (2), metoprolol (3) and talinolol (4) and their respective extraction by the gastointestinal tract (E(g. i.)) and liver E(h)...

All these compounds are moderately lipophilic and should show excellent ability to cross biological membranes by transcellular absorption. Propranolol, betaxolol and metoprolol all have minimal gut first-pass metabolism, as shown by the low value for E(g. i.). Metabolism and first pass effects for these compounds are largely confirmed to the liver as shown by the values for E(g. i.). In contrast talinolol shows high extraction by the gastrointestinal tract with low liver extraction [13]. These effects are illustrated graphically in Figure 3.9 which shows the bioavailability predicted from hepatic extraction contrasted with that seen in vivo in man. 

Noticeably propranolol, betaxolol and metoprolol are close or on the borderline for hepatic first-pass effects, whereas talinolol falls markedly below it. Talinolol has been shown to be a substrate for P-glycoprotein [14]. The effect of the urea function is of key importance within this change, as urea lacks a strong type I unit in terms of Seel-... 

Fig. 3.10 Structures of pafenolol and celiprolol, derivatives of the talinolol (see Figure 3.6) structure which show similar bioavailability characteristics.

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