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- W2187446413 abstract "SUMMARY Using ahigh-pressure liquid chromatographic assay,we measured serum amiodarone concentrations serially in122patients treated withamiiodarone for1.5-53 months(mean9.3months)for control ofrefractory symptomatic atrial or symptomatic andlife-threatening ventricular tachyarrhythmias. Theatrial tachyarrhythmias were successfully controlled in45of54patients (83%)during a mean follow-up of10.0months. Intheventricular tachyarrhythmia group,whichincluded 22survivors ofsudden cardiac death, 38of50patients (76%)responded toamiodarone during a mean follow-up of10.9months. Although the mean serum amiodarone concentration didnotdiffer between responders andnonresponders, eight responders relapsed whentheir serum concentration fell below1.0mg/I. Sideeffects resulted in withdrawal ofamiodarone inonly10of122patients (9%)despite a 30%overall incidence ofsideeffects. Central nervoussystem andgastrointestinal side effects became more frequent with serum concentrations > 2.5mg/l,although onlycentral nervous systemside effects achieved statistical significance. Absorption anddisposition kinetics ofa single oral800-mg doseofamiodarone were studied ineight patients. Serumvalues were measured for24 hours infive patients during maintenance therapy, and elimination kinetics after long-term therapy were evaluated inthree patients. Thetissue concentration of amiodarone wasdetermined intwopatients whodiedduring long-term amiodarone therapy andan attempt was madein14patients tocorrelate serum concentrations withdaily dosages during maintenance therapy. Thepharmacokinetics oforal amiodarone support thepractice of using highloading dosages until arrhythmiasuppression orapparent steady state isachieved (usually 2-4weeks), followed bylow-dose maintenance therapy (200400 mg onceaday)fortreatment ofsymptomatic atrial andventricular tachyarrhythmias. AMIODARONEhasbeenprogressively recognized as aremarkably effective typeIIIantiarrhythmic agent since itsintroduction in1967.1-9 Itwasfirst introduced asanantianginal drugbecause ofitscoronary and systemic vasodilator properties'0 andwaslater found to beaneffective antiarrhythmic agent. Rosenbaum et al22demonstrated theclinical efficacy ofamiodarone forawidevariety ofcardiac arrhythmias, including those complicating theWolff-Parkinson-White syndrome.European andAmerican investigators have confirmed amiodarone's efficacy forarrhythmias refractory toconventional agents.3 912However, oral dosing schedules arelargely empiric, having evolved fromearly incomplete kinetic dataindogsandhumaans'3 andcumulative clinical experience inhumans. Whether amiodarone's ineffectiveness innonresponders isduetoinsufficient dosing ortolackof response hasbeendifficult toassess because ofinadequate pharmacokinetic data. Similarly, therelationship between sideeffects andclinically therapeutic dosages andserumamiodarone concentrations hasnot beenestablished. Andreasen etal. 14andresearchers in ourlaboratory'5'7 haveestablished similar high-pressureliquid chromatographic (HPLC) assays foramiodarone and have attempted todelineate thepharmacokinetics ofamiodarone inpatients. Wehavedescribed apparent steady-state kinetics'6 andattempted tocorreFromtheDivision ofCardiovascular Medicine andDepartments of Pharmacy andClinical Pharmacy, University ofMassachusetts Medical" @default.
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- W2187446413 date "1983-01-01" @default.
- W2187446413 modified "2023-09-23" @default.
- W2187446413 title "Clinical Pharmacokinetics andEfficacy ofAmiodarone forRefractory Tachyarrhythmias" @default.
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- W2187446413 hasPublicationYear "1983" @default.
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