Carvedilol pharmacokinetics

Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and autonomic balance in heart failure Clin Pharmacol (2001) 41, 97-106. 

Zarghi, A. et al. 2007. Quantification of carvedilol in human plasma by liquid chromatography using fluorescence detection Application in pharmacokinetic studies. J Pharm BiomedAnal. 44 250. 

Fukumoto, K., Kobayashi, T., Komamura, K., Kamakura, S., Kitakaze, M., and Ueno, K. 2005. Stereoselective effect of amiodarone on the pharmacokinetics of racemic carvedilol. Drug Metab. Pharmacokinet. 20 423-427. 

Currently there is a trend toward the synthesis and large-scale production of a single active enantiomer in the pharmaceutical industry [61-63]. In addition, in some cases a racemic drug formulation may contain an enantiomer that will be more potent (pharmacologically active) than the other enantiomer(s). For example, carvedilol, a drug that interacts with adrenoceptors, has one chiral center yielding two enantiomers. The (-)-enantiomer is a potent beta-receptor blocker while the (-i-)-enantiomer is about 100-fold weaker at the beta-receptor. Ketamine is an intravenous anesthetic where the (+)-enantiomer is more potent and less toxic than the (-)-enantiomer. Furthermore, the possibility of in vivo chiral inversion—that is, prochiral chiral, chiral nonchiral, chiral diastereoisomer, and chiral chiral transformations—could create critical issues in the interpretation of the metabolism and pharmacokinetics of the drug. Therefore, selective analytical methods for separations of enantionmers and diastereomers, where applicable, are inherently important. 

Pharmacokinetic properties, e.g., no CNS entry of atenolol and nadolol long half-life of carvedilol and nadolol. 

Tenero, D. Boike, S. Boyle, D. Ilson, B. Fesniak, H.F. Brozena, S. Jorkasky, D. Steady-state pharmacokinetics of carvedilol and its enantiomers in patients with congestive heart failure. J. Clin. Pharmacol. 2000, 40, 844-853. 

Gehr, T.W. Tenero, D.M. Boyle, D.A. Qian, Y. Sica, D.A. Shusterman, N.H. The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency. Eur. J. Clin. Pharmacol. 1999, 55, 269-277. 

In healthy subjects, carvedilol 25 mg daily for 7 days had no effect on the pharmacokinetics of a single 15-mg dose of phenprocoumon given on day 5 phenprocoumon. ... 

Harder S, Brei R, Caspary S, Merz rc. Lack of a pharmacokinetic interaction between carvedilol and digitoxin or phenprocoumon. EurJ Clin Pharmacol (1993) 44, 583-6. 

No pharmacokinetic interaction was seen in a study in healthy subjects given a single 1.75-mg dose of gUbenclamide with carvedilol 25 mg daily for 6 days. ... 

Harder S, Merz PG, Rietbrock N. Lack of pharmacokinetic interaction between carvedilol and digitoxin, pheiprocoumon or gUbenclamide. Cardiovasc Drugs Ther (1993) 7 (Suppl 2), 447. 

The blood levels and pharmacokinetics of carvedilol were unaffected by cimetidine in one study. ... 

Orthostatic hypotension occurred when levosimendan was given with isosorbide mononitrate. The haemodynamic effects of levosimendan were not significantly altered by captopiil, carvedilol or other unnamed beta blockers, or felodipine. Levosimendan does not alter the effects of warfarin. Itraconazole does not alter the pharmacokinetics of levosimendan. Levosimendan appears not to interact adversely with alcohoL... 

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. 

Wermeling DP, Feild CJ, Smith DA, Chandler MHH, Clifton GD, Boyle DA. Effects of loi -term oral carvedilol on the steady-state pharmacokinetics of oral digoxin in patients with mild to moderate hypertension. Pharmacotherapy (1994) 14, 600-6. 

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