Amiodarone pharmacokinetics

In the USA, amiodarone is approved for oral and intravenous use to treat serious ventricular arrhythmias. However, the drug is also highly effective for the treatment of supraventricular arrhythmias such as atrial fibrillation. As a result of its broad spectrum of antiarrhythmic action, it is very extensively used for a wide variety of arrhythmias. Amiodarone has unusual pharmacokinetics and important extracardiac adverse effects. Dronedarone, an analog that lacks iodine atoms, is under investigation. 

The pharmacokinetics of saquinavir is modified by agents that alter isoenzyme CYP3A4 of the cytochrome P-450 system and P-glycoprotein transporter. It should not be administered with midazolam, triazolam and ergot derivatives. The plasma concentrations of saquinavir are lower when coadministered with efavirenz, nevirapine or rifampin. Ritonavir reverses the effects of nevirapine on saquinavir. The coadministration of astemizole, terfenadine, amiodarone, bepridil, quinidine, propafenone or flecainide with saquinavir is also not recommended due to its potential for serious and/or life-threatening reactions. 

Lesko LJ. Pharmcokinetic drug interactions with amiodarone. Clin Pharmacokinet 1989 17 130-140. 

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. 

Weiss, M., The anomalous pharmacokinetics of amiodarone explained by nonexponential tissue trapping, Journal of Pharmacokinetics and Biopharmaceutics, Vol. 27, No. 4, 1999, pp. 383-396. 

Pharmacokinetics Amiodarone is incompletely absorbed after oral administration. The drug is unusual in having a prolonged half-life of several weeks. Full clinical effects may not be achieved until 6 weeks after initiation of treatment. 

Note. For a review of the pharmacokinetics of amiodarone see R. Latini etal., Clin. Pharmacokinet., 1984, 9, 136-156. 

Pharmacokinetics. Amiodarone is effective given orally its enormous apparent distribution volume (701/kg) indicates that little remains in the blood. It is stored in fat and many other tissues and the t) of 54 days after multiple dosing signifies slow release from these sites (and slow accumulation to steady state means that a loading dose is necessary, see Table 24.1). The drug is metabolised in the liver and eliminated through the biliary and intestinal tracts. 

Latini R, Tognoni G, Kates RE. Clinical pharmacokinetics of amiodarone. Clin Pharmacokinet 1984 9(2) 136-56. 

Staiger C, Jauernig R, de Vries J, Weber E. Influence of amiodarone on antipyrine pharmacokinetics in three patients with ventricular tachycardia. Br J Clin Pharmacol 1984 18(2) 263. ... 

Lesko LJ. Pharmacokinetic drug interactions with amiodarone. Qin Pharmacokinet 1989 17(2) 130-40. 

Nolan PE Jr, Marcus FI, Karol MD, Hoyer GL, Gear K. Effect of phenytoin on the cUnical pharmacokinetics of amiodarone. J CUn Pharmacol 1990 30(12) 1112-19. 

The pharmacokinetics of procainamide are altered by amiodarone, with a reduction in clearance of about 25% due to changes in both renal and non-renal clearances (62). 

Windle J, Prystowsky EN, Miles WM, Heger JJ. Pharmacokinetic and electrophysiologic interactions of amiodarone and procainamide. Clin Pharmacol Ther 1987 41(6) 603-10. 

Riva E, Gerna M, Neyroz P, Urso R, Bartosek I, Guai-tani A. Pharmacokinetics of amiodarone in man. J Cardiovasc Pharmacol 1982 4 264-9. 

The pharmacokinetics of the antiarrhythmic agents are summarized in Table 17-4, and a nomogram for estimating effective dosages of the oral forms (except amiodarone) is shown in Fig. 17-5. Dosing recommendations for the intravenous forms are shown in Table 17-5. 

With warfarin, one is always concerned about pharmacodynamic and pharmacokinetic drug interactions. None of the antiarrhythmic drugs mentioned above are likely to cause a pharmacodynamic interaction with warfarin. However, amiodarone is a cytochrome P450 enzyme inhibitor and increases warfarin s antithrombotic effects. Patients taking both drugs usually need to decrease their dose of warfarin. 

Andreason, F., Agerback, H., and Byerregarrd, P, Pharmacokinetics of amiodarone after intravenous and oral administration, /. Clin. Pharmacol, 19 293-299,1981. 

Nolan, P. E. et al.. Single dose pharmacokinetics of amiodarone. Drug Intell. Clin. Pharm., 19 463 66, 1985. 

Zipes, D. P, Amiodarone electrophysiologic action, pharmacokinetics and clinical effects, J. Am. Coll. Cardiol, 3 1059-1065, 1984. 

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