Amiodarone plasma concentrations

Absorption - Following oral administration, amiodarone is slowly and variably absorbed bioavailability is approximately 50%. Maximum plasma concentrations are attained 3 to 7 hours after a single dose. Plasma concentrations with chronic dosing at 100 to 600 mg/day are approximately dose-proportional, with a mean 0.5 mg/L increase for each 100 mg/day. 

Hypersensitivity to any component of the product. Coadministration of nelfinavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (eg, amiodarone, quinidine, ergot derivatives, pimozide, midazolam, triazolam, lovastatin, simvastatin see Drug Interactions). 

Bromocriptine and the ergot analogues suppress prolactin activity and amiodarone can cause iodine-induced hypo- or hyperthyroidism. Lithium, which has a low toxicity threshold, passes freely into milk and significant plasma concentrations may occur in nursing infants. 

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. 

AMIODARONE DRUG DEPENDENCE THERAPIES-BUPROPION T plasma concentrations of amiodarone, with risk of toxic effects Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 Initiate therapy of these drugs at the lowest effective dose... 

CIMETIDINE, RANITIDINE ANTIARRHYTHMICS-AMIODARONE, FLECAINIDE, MEXILETINE, PROCAINAMIDE, PROPAFENONE Likely t plasma concentrations of these antiarrhythmics and risk of adverse effects Cimetidine inhibits CYP2D6-mediated metabolism of flecainide, mexiletine, procainamide and propafenone. Ranitidine is a much weaker CYP2D6 inhibitor. Cimetidine is a potent inhibitor of organic cation transport in the kidney, and the elimination of procainamide is impaired Monitor PR and BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Consider alternative acid suppression therapy... 

CANNABIS AMIODARONE Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption Be aware. Watch for signs of toxicity especially when cannabis use abruptly changes... 

AMPHETAMINES ANTIARRHYTHMICS -AMIODARONE t plasma concentrations of amphetamine, with risk of toxic effects Due to inhibition of CYP2D6-mediated metabolism of amphetamine Avoid concurrent use... 

GRAPEFRUIT JUICE AMIODARONE Markedly T plasma concentrations of amiodarone (AUC >50%, maximum concentration >84%). Possibly 1 effect of amiodarone (1 in P-R and Q-Tc intervals). This could lead to l therapeutic effect due to 1 production of active metabolite Due to inhibition of CYP3A4-mediated metabolism of amiodarone by grapefruit juice, which results in near-complete inhibition of the production of N-DEA (desethylamiodarone, the active and major metabolite of amiodarone) Warn patients to avoid grapefruit juice if amiodarone becomes less effective, ask the patient about grapefruit juice ingestion... 

During chronic treatment with 400 mg daily to 33 subjects, mean steady-state plasma concentrations of 2.2 pg/ml of amiodarone and 2.0 pg/ml of monodesethylamiodarone were reported (R. J. Flanagan et al., J. Pharm. Pharmac., 1982,34, 638-643). 

Loratadine is well absorbed after oral administration, with peak plasma concentrations at approximately 1.5 hours. Clinically significant relief of symptoms is usually obtained within 2 to 4 hours of the first dose. Excretion of loratadine occurs almost equally through the urine and feces.This dual mechanism of secretion provides a measure of safety in patients with liver or kidney disease, but caution should be exercised in both groups. Also, torsades de pointes may occur with the concurrent use of loratadine and amiodarone. Desloratadine is a metabolite of loratadine. 

The steady-state plasma concentrations of amiodarone and desethylamiodarone in 77 patients taking two... 

The authors suggested that torsade de pointes induced by intravenous amiodarone depended on heart rate during a bout of bradycardia, while that after oral amiodarone depended on increased sympathetic nervous system activity, and that therefore different electrophysiological mechanisms had been at play. However, it is by no means clear from their description of this case that that was so. They did not report plasma concentrations of amiodarone or desethylamiodarone, its active metabolite. 

Amiodarone increases the plasma concentrations of phenytoin, probably by inhibiting its metabolism (259,260), while phenytoin increases the metabolism of amiodarone and perhaps also of its metabolite desethylamiodarone (261). 

Sauro SC, DeCarolis DD, Pierpont GL, Gornick CC. Comparison of plasma concentrations for two amiodarone products. Ann Pharmacother 2002 36(ll) 1682-5. 

Amiodarone is slowly absorbed with an average bioavailabilty of 50% (range, 22-86%). Food has been shown to increase the rate and extent of absorption. Peak plasma concentrations are seen within 3-7 h (range, 2-12 h) however, the onset of action is not seen for at least 2-3 days and usually not until 1-3 weeks. This delay occurs even if a loading dose is given. Maximal responses may not occur until up to 5 months after starting therapy. Amiodarone is... 

Sotalol, Procainamide, Disopyramide, Dofetilide, Ibutilide, N oncardioacti ve , drugs (see text) Amiodarone (rare) interval (torsades de pointes) Isoproterenol Magnesium frequent Related to T plasma concentrations, except for quinidine... 

Two hundred milligrams of amiodarone contains 75 mg of iodine. Patients treated with the common daily dose of 200 mg amiodarone, get a load of 7 mg free iodide/ day, which is 35-times the daily recommended iodine dose. Amiodarone is lipophilic and concentrates in adipose tissue, cardiac and skeletal muscle, and in the thyroid (Daniels, 2001). The amiodarone plasma half life is approximately 52 23 days (Hermann, 2004). Typical changes in thyroid function are an increase in serum T4 and reverse triiodothyronine (rT3), and a decrease in serum T3 concentrations related to the inhibition of 5 -deiodinase-activity, resulting in a decrease in the generation of T3 from T4 and a decrease in the clearance of rT3 (Martino et al, 2001) and an inhibition ofT3 receptor binding and action (Daniels, 2001). 

Amiodarone is extensively bound to plasma proteins and is widely distributed throughout the body. The mean volume of distribution is 66 1/kg and ranges from 7 to 148 1/kg. Steady-state amiodarone serum concentrations range between 1 and... 

Zhang Z, Wang G, Wang H, Zhang J. Effect of amiodarone on the plasma concentration of aprindine [Abstract 115 197745u in Chemical Abstracts (1991) 115, 22]. Zhor uo YaoXue ZaZhi( 99 )26, 156-9. 

The hypothesis that the two excipients, benzyl alcohol and polysorbate 80, precipitated cardiogenic shock seems plausible, particularly because the plasma concentrations of amiodarone and desethylamiodarone never reached toxic concentrations. 

Pathophysiology Concentrations of amio-darone and desethylamiodarone were measured simultaneously in plasma and fat in 30 patients who had taken amiodarone for 3 months to 12 years [38 ]. Amiodarone concentrations in fat were 4—226 (mean 55) times higher than in plasma, and correlated with plasma concentrations (r = 0.68). Nine of 12 patients who had taken amiodarone for at least 2 years developed clinically important adverse reactions, predominantly hypothyroidism (n = 6), compared with two of 18 patients who had taken it for less time (RR = 6.75 95% Cl = 1.8, 26). The risk of adverse reactions did not correlate with amiodarone concentrations in plasma or fat. 

A retrospective study in a 73-patient cohort showed that the addition of amiodarone, an antiarrhythmic medication, resulted in highly variable changes in warfarin dose requirements. Metabolites of amiodarone in human plasma were quantified by a liquid chromatography-electrospray ionization-tandem mass spectrometry assay, and inhibition constants (Kj) were determined for the inhibition of (S)-warfarin 7-hydroxlylation in human liver micro-somes. By calculating the ratios of unboxmd plasma concentrations to the microsomal Kj for the unbound drug, a minor metabolite of amiodarone, N,N-didesethylamiodarone, was identified as a major contributor to the interaction between amiodarone and warfarin [11 ]. 

Quinidine inhibits the tubular secretion of digoxin which consequently raises the plasma digoxin concentration, which may be associated with toxicity. Certain other drugs also increase the digoxin concentration like verapamil, amiodarone, spironolactone etc. 

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