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PubMed1992

[Efficacy of intravenous and per os propafenone in the ambulatory treatment of recent-onset atrial fibrillation].

Propafenone efficacy in conversion of atrial fibrillation to sinus rhythm has been well documented. In this study we considered propafenone efficacy according to a graduated protocol of administration. Forty-two patients with recent-onset atrial fibrillation, without left ventricular failure, ischemic symptoms and in absence of antiarrhythmical treatment, were treated according to the following protocol: propafenone 1 mg/kg i.v. (5 min) followed, in the non-responder patient group, by a second dose, 0.5 mg/kg i.v. (15 min). Patients with persistent atrial fibrillation received 900 mg/daily of propafenone per os, at home for two days. Thereafter, patients still not restored to sinus rhythm were considered non-responders. Patients who were converted to sinus rhythm received 450 mg daily of the drug (oral administration), at home, as antiarrhythmical prophylaxis, for three months. Thirty-nine patients were converted to sinus rhythm (92.8%), 24 of them after intravenous propafenone (57.2%), and the other 15 (35.6%) after oral administration of the drug. The average heart rate in patients not converted to sinus rhythm with intravenous propafenone was significantly reduced after drug administration, compared to basal values (from 136.4 +/- 18.1 to 107.1 +/- 17.6, p < 0.01), allowing home treatment. No major cardiac effects were observed after infusion, nor after oral administration of propafenone. During a three-month follow-up we observed 3 cases of relapsed atrial fibrillation and 2 discontinued treatments due to minor gastroenteric side effects. In conclusion, propafenone therapy in ambulatory regimen is safe and effective in patients with recent-onset atrial fibrillation. In many patients refractory to IV treatment, further therapeutic success may be achieved following oral propafenone administration.

Administration, Oral↗
PubMed2003

Concentration dependent stereoselectivity of propafenone N-depropylation metabolism with human hepatic recombinant CYP1A2.

Concentration dependency of stereoselective N-depropylation metabolism of propafenone was studied by using transgenic cell line expressing human CYP1A2. Enantiomers of propafenone and N-depropylpropafenone were separated and assayed simultaneously by RP-HPLC with precolumn GITC chiral derivatization. The experimental results showed that CYP1A2 was involved in enantioselective N-depropylation of propafenone and that the metabolic stereoselectivity depends on substrate concentration. For racemic propafenone, stereoselectivity was observed at low substrate concentration and was not seen at high substrate concentration. For individual isomers, S-(+)-propafenone was metabolized faster than its antipode at higher enantiomer concentrations and R-(-)-propafenone was eliminated faster than its antipode at lower enantiomer concentrations. There is interaction between S- and R-propafenone. R-(-)-propafenone inhibited the metabolism of S-(+)-propafenone with IC50 0.225 mmol/L for human CYP1A2.

Anti-Arrhythmia Agents↗
PubMed1991

Propafenone disposition and pharmacodynamics in normal and norepinephrine-induced cardiomyopathic rabbit hearts.

The myocardial disposition and pharmacodynamics of propafenone were studied in 10 normal and 10 norepinephrine-induced cardiomyopathic rabbit hearts. The left ventricular propafenone concentrations measured after perfusion of propafenone (0.3 microM) for 150 min were similar in the normal group (18 +/- 8 micrograms/g) compared to the cardiomyopathy group (20 +/- 5 micrograms/g, P = NS). However, the concentration of propafenone in cardiomyopathic left ventricular papillary muscle, which was always extensively involved in the inflammatory process, was significantly lower (11 +/- 2 micrograms/g) compared to normal papillary muscle (19 +/- 4 micrograms/g, P less than .05). During propafenone perfusion a significantly greater increment in ventricular conduction time was observed in the cardiomyopathy group (17 +/- 6 msec) compared to the normal group (12 +/- 3 msec, P less than .05). The propafenone myocardial concentration-effect relationships describing changes in QRS duration were shifted to the left in the cardiomyopathy group. Furthermore, the slopes of these linear concentration-effect relationships were greater in the cardiomyopathy group (1.80 +/- 0.60 msec/micrograms/g) compared to the normal group (1.07 +/- 0.25 msec/micrograms/g, P less than .01). The ventricular effective refractory period was shorter at base line in the cardiomyopathy hearts (156 +/- 21 msec) compared to the normal group (176 +/- 23 msec, P less than .08). However, propafenone effects on changes in the ventricular effective refractory period were similar in the two groups. Thus, the myocardial accumulation of propafenone is reduced in areas of extensive necrosis observed in norepinephrine-induced cardiomyopathy. As well, cardiomyopathic tissue is more responsive to propafenone effects on ventricular conduction time.

Animals↗
PubMed1991

Antiarrhythmic effects of two new propafenone related drugs. A study on four animal models of arrhythmia.

LG 6-101 (1-[3-(2-methoxy-3-(2-methylpropylamino)-propoxy)-4-methyl- 2-thienyl]-3-phenyl-1-propanone, hydrochloride) and LG 6-102 (2-(2-methoxy-3-propylamino-propoxy)-3-phenyl-propiophenone, hydrochloride) are two new antiarrhythmic drugs. They are structurally related to propafenone which is a widely used class 1 antiarrhythmic drug with relatively low bioavailability. Both substances were characterized in four animal models of arrhythmia and compared to propafenone. In isolated guinea pigs left auricles LG 6-101 and LG6-102 were about twice as effective as propafenone regarding the prolongation of the functional refractory period but did not decrease contractility more than propafenone. LG 6-101 was significantly more effective (p less than or equal to 0.002) than propafenone or LG 6-102 in delaying the onset of ventricular premature beats in ouabain induced arrhythmias in guinea pigs. In aconitine induced arrhythmias in rats, LG 6-101 and LG 6-102 did not differ in their antiarrhythmic effects from propafenone, whereas the protection against cardiac arrest was significantly (p less than or equal to 0.003) better for LG 6-101 than for propafenone or LG 6-102. In arrhythmias induced by occlusion of the left descending coronary artery in rats the drugs tested showed as good antiarrhythmic effects as propafenone. In this model the size of the ischemic area was also measured and LG 6-101 was the most effective drug in that respect. These results suggest that both LG 6-101 and LG 6-102 are potent antiarrhythmic substances which in some models were more effective than propafenone.

Aconitine↗
PubMed2000

Stereoselective determination of propafenone enantiomers in transgenic Chinese hamster CHL cells expressing human cytochrome P450.

An enantioselective assay for S(+)- and R(-)-propafenone in transgenic Chinese hamster CHL cells expressing human cytochrome P450 was developed. The method involved extraction of propafenone from the S9s incubates, and formation of propafenone diastereomeric derivatives with the chiral reagent 2,3,4, 6-tetra-O-beta-D-glucopranosyl isothiocyanate. Separation and quantitation of diastereomeric propafenone derivatives were carried out in a reverse-phase-HPLC system with UV detection. The assay was linear from 2 to 200 microg/mL for each enantiomer. The analytical method gave average recoveries of 97.5% and 97.0% for S(+)- and R(-)-propafenone, respectively. The limits of detection and quantitation for the method are 0.1 and 2.0 microg/mL for both S(+)- and R(-)-propafenone, respectively. The reproducibility of the assay was good (RSD <10%). The method allowed study of the depletion of S(+)- and R(-)-propafenone in transgenic Chinese hamster CHL cells expressing human cytochrome P450. The stereoselectivity of propafenone phase I metabolism via cDNA-expressed CYP3A4 was observed.

Animals↗
PubMed1995

Influence of renal function on the steady-state pharmacokinetics of the antiarrhythmic propafenone and its phase I and phase II metabolites.

The aim of this study was to investigate the disposition of propafenone and its Phase I and II metabolites in relation to kidney function under steady-state conditions. The mechanism of the renal handling of propafenone glucuronides (filtration, secretion) was also examined. Racemic (R/S) propafenone was administered to 7 young volunteers, to 5 older patients with a normal glomerular filtration rate and to 4 patients with chronic renal failure. No difference was found in the plasma concentrations of propafenone and 5-hydroxypropafenone between the three groups. The propafenone glucuronide (PPFG) concentration was elevated in the older compared to the younger subjects (S-PPFG: 544 vs. 222 nmol.ml-1.mol-1; R-PPFG: 576 vs. 304 nmol.ml-1.mol-1). Although Glomerular filtration rate did not differ, the renal clearance of propafenone glucuronides was reduced in the former group, which could be attributed to their impaired renal secretion. A dramatic increase in propafenone glucuronide concentration was observed in the patients with renal failure (S-PPFG: 2783 nmol.ml-1.mol-1; R-PPFG: 7340 nmol.ml-1.mol-1). In summary, the disposition of propafenone and of its active metabolite 5-hydroxypropafenone was not affected by kidney dysfunction, indicating that no dose adjustment is necessary in patients with renal failure. The accumulation of drug glucuronides in older patients with apparently normal kidney function should be taken into account as a possible factor modifying drug therapy.

Aged↗
PubMed1988

Pharmacokinetics and pharmacodynamics of propafenone during acute and chronic administration.

The pharmacokinetics of propafenone and 5-OH-propafenone and their relationship with the antiarrhythmic action and side effects have been studied in 10 patients with stable, frequent, premature ventricular beats (224-928 premature ventricular complexes/h). Observations were made after a single dose of propafenone 300 mg p.o., and after 1 and 3 months (only 5 out of 10 patients) of therapy with 300 mg t.d.s. After 1 month of treatment the plasma elimination half-life of propafenone (6.7 h) was almost twice as long as after a single dose (3.5 h), and the area under the plasma propafenone concentration-time curve (7620 ng.ml-1.h) was significantly larger than after single dose (3522 ng.ml-1.h); this was also true for the metabolite. The ratio of the AUCs of 5-OH-propafenone and propafenone decreased from the single dose (0.63) to 1 month (0.32). These variables remained stable up to 3 months. Eight patients had greater than or equal to 75% reduction of premature ventricular complexes after 3 days of therapy, and in 7 they were completely suppressed; the response was maintained over 1 to 3 months. Side effects were minor and in no case had the drug to be withdrawn or the dose reduced. Thus, the kinetics of propafenone were time-dependent. Its active metabolite did not accumulate greatly during chronic treatment. The lasting antiarrhythmic effect observed in some patients suggests a b.d.s. regimen instead of t.d.s. dosing in selected patients.

Adult↗
PubMedDate not supplied

The metabolic fate of 2H-labelled propafenone in man.

The metabolism of propafenone was studied in three humans by using 300 mg of the deuterated compound given orally. The excretion of propafenone and its metabolites was assessed by measuring the deuterium content in the excretion products by means of a microwave plasma detector. At selected times the metabolic pattern in plasma, urine, bile and feces was determined. The metabolites were isolated and the structure of the main compounds was characterized. Propafenone is absorbed completely and quantitatively metabolized. Unchanged propafenone is excreted neither in the urine nor in the feces in amounts of more than 1% the dose. The percentage of free unconjugated propafenone of the total deuterium content in the plasma was about 10% 3 and 6 hours after application. Conjugates of hydroxylated derivatives of propafenone are present predominantly in the plasma. The excretion of the metabolites takes place mainly by way of the feces, 53% of the dose is excreted by this route within 48 hours. Urinary elimination accounted for 18.5 and 38% of the dose within 48 hours in two humans. It was possible to elucidate the structure of 11 metabolites, accounting for more than 90% of the dose administered. The major metabolites are conjugates of 5-hydroxypropafenone and hydroxy-methoxy-propafenone with glucuronic and sulphuric acid and propafenone glucuronide. Furthermore, metabolic products of oxydative deamination pathway were identified, i.e. a glycol and a lactic acid derivative. C-C splitting yields a relatively large amount of 3-phenyl-propionic acid, while cleavage of the ether group leads to a phenolic product and is only of minor importance.

Administration, Oral↗
PubMed1984

Electrophysiologic effects of propafenone on canine ischemic cardiac cells.

The electrophysiologic effects of propafenone were studied by conventional microelectrode techniques in ischemic myocardial and Purkinje fibers from 1-day-old myocardial infarction in the dog. Propafenone reduced the amplitude and rate of rise of normal myocardial and Purkinje action potentials and had little effect on the resting potential. In the control state, both ischemic myocardial and Purkinje fibers had reduced resting potential, action potential amplitude and upstroke velocity. These fibers were more susceptible to the depressant effects of propafenone than normal fibers. Ischemic myocardial fibers were particularly sensitive to the actions of propafenone that resulted in marked depression of action potential characteristics, with little effect on resting potential. These changes resulted in cycle length-dependent conduction disorders in ischemic epicardial preparations. However, in ischemic endocardial preparations in which triggered activity could be initiated, propafenone reversibly suppressed the triggered activity. Termination of the triggered activity was preceded by slowing of the rate, which was attributed to a decrease in the rate of rise of the delayed afterdepolarizations. This activity terminated when the delayed afterdepolarization failed to attain threshold potential. This study suggests that propafenone has a membrane-anesthetic effect, with the abnormal fast channel in ischemic cells being more sensitive; propafenone depresses delayed afterdepolarizations in ischemic Purkinje fibers; and the actions of propafenone could result in an antiarrhythmic effect in vivo on both reentrant ventricular rhythms in ischemic myocardium and triggered rhythms in ischemic Purkinje fibers.

Action Potentials↗
PubMed1989

Usefulness of propafenone for recurrent paroxysmal atrial fibrillation.

To evaluate the efficacy of propafenone for suppression of recurrent paroxysmal symptomatic atrial fibrillation (AF), patients with frequent episodes of AF entered an open-label, dose-ranging study to determine the maximal tolerated dose of propafenone and were subsequently randomized to alternate between propafenone and placebo every month for 4 months. Patients recorded each episode of AF in a diary and recorded a simultaneous electrocardiographic rhythm strip by means of a transtelephonic recorder and transmitter to validate the presence of AF. Eighteen patients were eligible for study. During dose ranging, 4 patients withdrew due to inadequate drug efficacy or poor compliance, 2 withdrew due to intolerable side effects and 1 died. The mean dose of propafenone at the end of dose ranging was 644 +/- 189 mg/day. During the crossover study, the percentage of days with an attack of AF was significantly reduced by propafenone compared with placebo (27 +/- 34 vs 51 +/- 34%, p less than 0.01). The rate of early crossover or withdrawal from the crossover study was 13.6% with propafenone and 45% with placebo (p = 0.056). Five patients went on to receive long-term propafenone and 4 continued treatment with suppression of AF for 12 to 21 months. During the crossover study there were 29 reported minor side effects with propafenone and 11 with placebo.

Anti-Arrhythmia Agents↗
PubMed1992

Acute pharmacologic conversion of atrial fibrillation and flutter: the role of flecainide, propafenone, and verapamil.

Efficacy and safety of intravenous flecainide (2 mg/kg body weight in 10 minutes), verapamil (10 mg in 1 minute), and propafenone (2 mg/kg body weight in 10 minutes) were investigated in 90 consecutive patients with atrial fibrillation (AF) or flutter (AFL). In the first 40 patients, flecainide and verapamil were evaluated; in the second 50 patients, flecainide and propafenone were compared, both in a single-blind randomized study design. The primary end point was sinus rhythm occurring within 1 hour after start of infusion. Sinus rhythm was attained in 32 of 37 patients (86%) with AF treated with flecainide and in 11 of 20 patients (55%) with AF treated with propafenone. In recent onset AF (less than or equal to 24 hours) conversion rates were 24 of 25 patients (96%) in the flecainide group and 8 of 14 patients (57%) in the propafenone group (p less than 0.05). Conversion of AFL occurred in only 1 of 8 patients (13%) in the flecainide-treated patients and in 2 of 5 patients (40%) treated with propafenone (difference not significant). Verapamil was almost ineffective, since only 1 of 20 patients (5%) responded within 1 hour. Time to conversion was 21 +/- 17 minutes in the flecainide group and 16 +/- 10 minutes in the propafenone group. QRS widening occurred in flecainide-treated patients (83 +/- 15 to 99 +/- 20 msec; p less than 0.001), but not after propafenone (83 +/- 11 to 86 +/- 12 msec). Significantly higher plasma levels were found in patients with conversion within 1 hour using propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗
PubMed2004

Ibutilide added to propafenone for the conversion of atrial fibrillation and atrial flutter.

OBJECTIVES: We evaluated the safety and efficacy of ibutilide when added to propafenone in treating both paroxysmal and chronic atrial fibrillation (AF) and atrial flutter (AFL). BACKGROUND: The effects of ibutilide in patients with paroxysmal or chronic AF/AFL who were pre-treated with propafenone have not been previously evaluated. METHODS: Oral propafenone was initially given in 202 patients with AF/AFL without left ventricular dysfunction. Intravenous ibutilide was administered in 104 patients in whom propafenone failed to convert the arrhythmia. Two different propafenone dosage regimens were used according to the duration of the presenting arrhythmia: patients with paroxysmal arrhythmia (n = 48) received 600 mg loading dose, and patients with chronic arrhythmia (n = 56) were receiving 150 mg three times a day as stable-dose pre-treatment. RESULTS: Ibutilide offered an overall conversion efficacy of 66.3% (69 of 104 patients), 70.8% for patients with paroxysmal AF/AFL and 62.5% for patients with chronic AF/AFL. Ibutilide significantly decreased the heart rate (HR) and further prolonged the QTc interval (p < 0.0001). The degree of HR reduction after ibutilide administration emerged as the sole predictor of successful arrhythmia termination (p < 0.001). After ibutilide, one patient (1%) developed two asymptomatic episodes of non-sustained torsade de pointes, and 10 patients (9.6%) manifested transient bradyarrhythmic events; however, all bradyarrhythmic effects were predictable, occurring mostly at the time of arrhythmia termination. None of 82 patients who decided to continue propafenone after successful cardioversion had immediate arrhythmia recurrence. CONCLUSIONS: Our graded approach using propafenone and ibutilide appears to be a relatively safe and effective alternative for the treatment of paroxysmal and chronic AF/AFL to both rapidly restore sinus rhythm in nonresponders to monotherapy with propafenone and prevent immediate recurrences of the arrhythmia.

Administration, Oral↗
PubMed2001

Long-term efficacy and safety of propafenone and sotalol for the maintenance of sinus rhythm after conversion of recurrent symptomatic atrial fibrillation.

This study was performed to evaluate, using a randomized double-blind, placebo-controlled protocol, the long-term efficacy and safety of propafenone and sotalol in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation (AF). The maintenance of sinus rhythm in patients with recurrent AF has several potential benefits, the most important being a reduced risk of thromboembolic events. Three hundred patients with recurrent AF (> or = 4 episodes in the last year) and AF at enrollment lasting < 48 hours were randomized to receive either propafenone (mean daily dose 13 +/- 1.5 mg/kg; 102 patients), sotalol (mean daily dose 3 +/- 0.4 mg/kg; 106 patients), or placebo (92 patients). After 1-year follow-up, Kaplan-Meier estimates of the proportion of patients remaining in sinus rhythm were comparable between propafenone (63%) and sotalol (73%) and superior to placebo (35%; p = 0.001 vs both drugs). Symptomatic recurrences occurred later with propafenone and sotalol than with placebo. Nine patients (9%) in the propafenone group, 11 (10%) in the sotalol group, and 3 (3%) in the placebo group discontinued therapy due to adverse effects. Malignant nonfatal arrhythmias due to proarrhythmic effects were documented with sotalol only, and occurred < 72 hours from the beginning of therapy in 4 patients (4%). During recurrences, the ventricular rate was significantly reduced in patients taking propafenone and sotalol (p = 0.001 for both drugs vs placebo). The likelihood of remaining in sinus rhythm during follow-up was higher in younger patients with smaller left atrial size and without concomitant heart disease. In patients with recurrent symptomatic AF, propafenone and sotalol are not significantly different from each other and are superior to placebo in maintaining sinus rhythm at 1 year. Recurrences occur later and tend to be less symptomatic with propafenone and sotalol compared with placebo.

Administration, Oral↗
PubMed1984

Propafenone treatment of recurrent ventricular tachycardia: comparison of continuous electrocardiographic recording and electrophysiologic study in predicting drug efficacy.

Propafenone was administered to 29 patients who had multiple episodes of recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) despite previous antiarrhythmic therapy. All patients had 24-hour continuous electrocardiographic recording and electrophysiologic study in a drug-free control state and while receiving maximum doses of propafenone. During propafenone treatment, the mean frequency of ventricular premature complexes (VPCs) decreased 74% (p less than 0.05). There was more than an 83% decrease in VPC frequency in 17 of 29 patients, and 11 patients had 99 to 100% decreases. Propafenone prevented VT induction at electrophysiologic study in 6 patients, whereas another 12 patients were judged to have satisfactory electrophysiologic responses on the basis of slower VT rates and absence of hemodynamic compromise during VT. After long-term treatment from 2 to 26 months, 9 patients continued propafenone without evidence of recurrent arrhythmia. Six of these 9 patients had not VT induction at electrophysiologic study while receiving propafenone. The decrease in VPC frequency produced by propafenone was a poor predictor of a successful electrophysiologic study and of long-term therapy. In conclusion, propafenone has potential as an effective antiarrhythmic agent, but better methods to stratify risk for recurrence of VT and VF are needed.

Adult↗
PubMed1996

Cardiac electrophysiological effects of propafenone and its 5-hydroxylated metabolite in the conscious dog.

We studied the cardiac electrophysiological effects of propafenone and its 5-hydroxylated metabolite in conscious dogs. Sinus rate, corrected sinus recovery time and Wenckebach point were measured in 6 intact dogs. Atrial rate, ventricular rate and atrial effective refractory period were measured in 6 atrioventricular-blocked dogs. In both groups, we also determined blood pressure and plasma drug concentrations. Each dog received, with at least an 8-day interval, propafenone (hydrochloride) and 5-hydroxypropafenone (hydrochloride) in 4 successive intravenous injections, 30 min apart, at 0.5, 0.5, 1 and 2 mg kg(-1). Propafenone increased sinus rate and atrial rate more markedly than 5-hydroxypropafenone, and also transiently ventricular rate, whereas 5-hydroxypropafenone decreased it weakly. Propafenone shortened corrected sinus recovery time and increased Wenckebach point at the highest dose only, whereas 5-hydroxypropafenone did not modify corrected sinus recovery time and increased Wenckebach point less markedly than propafenone. Both drugs produced an identical atrial effective refractory period lengthening. Propafenone either increased mean blood pressure (in intact dogs) or decreased it (in atrioventricular-blocked dogs) at the highest dose only, whereas 5-hydroxypropafenone did not produce any effect on this parameter. Overall, these results show that propafenone and 5-hydroxypropafenone exhibit cardiac electrophysiological effects, reflecting (a) direct vagolytic action for both drugs associated with cardiodepressant effects for 5-hydroxypropafenone, and (b) marked atrial antiarrhythmic properties for 5-hydroxypropafenone probably involved in the therapeutic effect of propafenone.

Animals↗
PubMed1999

Safety of oral propafenone in the conversion of recent onset atrial fibrillation to sinus rhythm: a prospective parallel placebo-controlled multicentre study.

AIM: Oral propafenone is effective in restoring sinus rhythm however the proarrhythmic effects are still unknown. The Safety Antiarrhythmic Therapy Evaluation (SATE) trial was a prospective randomized placebo-controlled multicentre study which evaluated the safety of acute oral loading dose of propafenone in patients with recent onset atrial fibrillation. Secondary end-points were to evaluate the effect of digitalis added to propafenone in ventricular rate control and the efficacy of propafenone alone or added to digitalis compared with efficacy of digitalis plus quinidine. METHODS AND RESULTS: 246 patients (126 male; 58+/-11 years) with atrial fibrillation of <48 h duration were randomly allocated to one of four groups: digitalis 0.75-1 mg i.v. plus quinidine 1100 mg (D+Q, 70 patients); propafenone 450-600 mg orally (PNF, 66 patients); propafenone 450-600 mg orally plus digitalis 0.750-1 mg i.v. (PNF+D, 70 patients); placebo (Pl, 40 patients). All patients underwent 24-h ECG Holter monitoring. Safety was assessed by evaluating the appearance of adverse events classified as mild, moderate and severe. No severe adverse events were reported. Short lasting asymptomatic atrial flutter episodes with atrio-ventricular conduction > or =2:1 were observed in 14% of the D+Q group, 21% PNF, 18% PNF+D and in 8% Pl. One patient in the D+Q group and four in the PNF+D group showed asymptomatic runs of 3-4 ventricular ectopic beats. Reversible sinus atrial blocks (<3 s) were detected in two patients of the D+Q group and in two of the PNF group. In patients with persistent atrial fibrillation the ventricular rate was similar in the four study groups. At 3 h the high efficacy of propafenone was confirmed. At the 24th hour no differences were found between active treatment and placebo arms. CONCLUSION: Propafenone in a single oral loading dose is safe and promptly effective in patients with recent onset atrial fibrillation.

Administration, Oral↗
PubMed1998

Kinetics of buccal absorption of propafenone single oral loading dose in healthy humans.

Buccal absorption has an advantage when compared with other administration routes because of its rapid onset of action. We examined the pharmacokinetics of buccal-absorbed propafenone in healthy humans. 1. After a single oral administration of 150 mg of propafenone, the average peak concentration of propafenone was 27.9+/-2.5 ng/ml, and that of 5-hydroxypropafenone was 61.7+/-6.6 ng/ml (n=5). The times to reach peak serum concentrations of propafenone and 5-hydroxypropafenone were 1.8+/-0.1 hr and 1.5+/-0.2 hr, respectively. 2. After a buccal absorption of 150 mg of propafenone, the time to reach peak serum concentration of propafenone was 16.9+/-2.3 min (n=8). The average peak concentration of propafenone was 30.4+/-1.4 ng/ml (n=8), and the concentrations of 5-hydroxypropafenone were below the detection limit in all subjects. The rapid upstroke of serum concentrations of propafenone by buccal administration may cause rapid onset of pharmacological conversion.

Absorption↗
PubMed2000

Determination of propafenone and its phase I and phase II metabolites in plasma and urine by high-performance liquid chromatography-electrospray ionization mass spectrometry.

A sensitive method was developed to determine propafenone, 5-hydroxypropafenone, N-despropylpropafenone and propafenone glucuronides in human plasma and urine by HPLC-electrospray ionization mass spectrometry with the respective deuterated analogues as internal standards. The analytes were extracted by a single solid-phase extraction, collecting two fractions, one containing the glucuronides and the other propafenone and the phase I metabolites 5-hydroxypropafenone and N-despropylpropafenone. The mobile phases used for HPLC were: (A) 5 mM ammonium acetate in water and (B) 5 mM ammonium acetate in methanol-tetrahydrofuran (50:50, v/v). Separation of the diastereoisomeric propafenone glucuronides was achieved on a Spherisorb ODS 2 column (150 x 2.0 mm I.D., particle size 5 microm) at a flow-rate of 0.3 ml/min using a linear gradient from 20% B to 50% B in 15 min. For separation of propafenone, 5-hydroxypropafenone and N-desalkylpropafenone a linear gradient from 50% B to 80% B in 10 min was employed. The mass spectrometer was operated in the selected ion monitoring mode using the respective MH+ ions for quantification. The limits of quantification achieved with this method were 10 pmol/ml for propafenone, 5-hydroxypropafenone, R- and S-propafenone glucuronide and 20 pmol/ml for N-desalkylpropafenone using 0.5 ml of plasma. Reproducibility and accuracy was below 12% for each analyte over the whole concentration range measured. The method was applied to a pharmacokinetic study assessing the influence of rifampicin on propafenone disposition.

Chromatography, High Pressure Liquid↗