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SUMMARY Using a high-pressure liquid chromatographic assay, we measured serum amiodarone concentrations serially in 122 patients treated with amiiodarone for 1.5-53 months (mean 9.3 months) for control of refractory symptomatic atrial or symptomatic and life-threatening ventricular tachyarrhythmias. The atrial tachyarrhythmias were successfully controlled in 45 of 54 patients (83%) during a mean follow-up of 10.0 months. In the ventricular tachyarrhythmia group, which included 22 survivors of sudden cardiac death, 38 of 50 patients (76%) responded to amiodarone during a mean follow-up of 10.9 months. Although the mean serum amiodarone concentration did not differ between responders and nonresponders, eight responders relapsed when their serum concentration fell below 1.0 mg/I. Side effects resulted in withdrawal of amiodarone in only 10 of 122 patients (9%) despite a 30% overall incidence of side effects. Central nervous system and gastrointestinal side effects became more frequent with serum concentrations > 2.5 mg/l, although only central nervous system side effects achieved statistical significance.Absorption and disposition kinetics of a single oral 800-mg dose of amiodarone were studied in eight patients. Serum values were measured for 24 hours in five patients during maintenance therapy, and elimination kinetics after long-term therapy were evaluated in three patients. The tissue concentration of amiodarone was determined in two patients who died during long-term amiodarone therapy and an attempt was made in 14 patients to correlate serum concentrations with daily dosages during maintenance therapy. The pharmacokinetics of oral amiodarone support the practice of using high loading dosages until arrhythmia suppression or apparent steady state is achieved (usually 2-4 weeks), followed by low-dose maintenance therapy (200400 mg patients (10 in the atrial group). During long-term amiodarone therapy (range 1.5-53 months, mean 9.3 months), antiarrhythmic agents were taken concomnitantly by five patients (quinidine in three, disopyramide in one and mexiletine in one). The patiehts were 22-93 years old (mean 56.2 years). No patient was excluded from the study based on renal, hepatic or cardiac function. In the atrial group, the underlying diagnoses were idiopathic atrial arrhythmias in 15 patients, sick sinus syndrome in 11,. valvular heart disease in 12, coronary artery disease in 10, and hypertensive heart disease in two. Forty-six of 68 patients in the ventricular group had coronary artery disease and previous myocardial infarction and 43 (63%) had evidence of left ventricular failure.

Propofol is generally efficacious in treating postoperative nausea and vomiting at plasma concentrations that do not produce increased sedation. Simulations indicate that to achieve antiemetic plasma propofol concentrations of 343 ng/ml, a bolus dose of 10 mg followed by an infusion of approximately 10 microg x kg(-1) x min(-1) are necessary.