Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:41708-72-9 (Tocainide)
 93 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tocainide, an oral form of lidocaine, was employed in 120 patients with recurrent malignant ventricular arrhythmia refractory to conventional antiarrhythmic drugs. After discontinuation of all antiarrhythmic agents, patients underwent control studies including 48 hours of ambulatory electrocardiographic monitoring and maximal symptom-limited exercise testing. One hundred patients had frequent as well as repetitive ventricular premature beats whereas in 20 patients, because of infrequency of ectopic activity, invasive electrophysiologic studies were carried out to provoke a repetitive ventricular response. Tocainide therapy was begun at 1,200 mg daily and increased to 2,400 mg daily guided by drug efficacy and the occurrence of adverse effects. After 48 hours of treatment with a fixed dose, drug action was evaluated by repeat monitoring and exercise stress testing or electrophysiologic testing. Fifty-five patients (46 percent) responded to tocainide. The average daily dose of drug and peak blood levels were equivalent in responders and nonresponders. Adverse effects occurred in 42 patients (35 percent) and were primarily related to the central nervous system. Lidocaine predicted the response to tocainide in 78 percent of patients. Thirty-four patients were continued on long-term maintenance therapy. After an average follow-up period of 16 months (range 2 to 39), treatment with the drug was discontinued in nine patients. The remaining 25 patients have had no adverse effects and no recurrence of ventricular arrhythmia.
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PMID:Tocainide for refractory symptomatic ventricular arrhythmias. 680 55

Tocainide is a primary amine with antiarrhythmic properties derived from lidocaine. For biopharmaceutical and pharmacokinetic purposes an assay was developed that made use of Schiff base formation with methyl isobutyl ketone and gas chromatography with nitrogen-selective detection. The derivatization procedure was performed at 85 C for 10 min, although a longer time at this temperature caused degradation of the product. Of several structural analogues the p-methyl one was the internal standard of choice. The amine was extracted from alkaline samples with dichloromethane and, after evaporation, reconstituted in methyl isobutyl ketone. From plasma the yields were lower than those from aqueous samples but the addition of hydroxylamine 30 min before the extraction process resulted in the same yields. Hydroxylamine probably acts as a competitor for carbonyl groups in the biological sample. In addition to the enhanced yields patients' samples extracted after hydroxylamine treatment were analysed with better precision. With nitrogen-selective detection 500 nmol/l in a 0.5-ml sample could be quantified, which is well below the therapeutic levels. The method compared favourably with a liquid chromatography assay.
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PMID:Determination of tocainide in human plasma by gas chromatography with nitrogen-selective detection after Schiff base formation. 680 1

Intravenous (IV) injection of lidocaine was used in patients with tinnitus for combined treatment with oral anticonvulsants carbamazepine (Tegretol) and primidone (Mysoline). In most cases, the high complication rate with these drugs precluded their long-term use. Tocainide hydrochloride (HCl), a primary amine analog of lidocaine, can be taken orally and was evaluated for the use in the treatment of tinnitus. A double-blind study in which one group received 200 mg tocainide HCl four times a day and one group received a placebo revealed no significant differences in tinnitus relief between the two groups. A single-blind study in which 600 mg tocainide HCl four times a day was administered showed 80% to 98% tinnitus relief in five of the six patients who tolerated the drug. Tocainide HCl treatment of tinnitus is promising.
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PMID:Treatment of tinnitus with tocainide hydrochloride. 682 29

Tocainide is structurally related to lidocaine but may be used orally as well as intravenously. A therapeutic plasma concentration range of 25 to 45 mumole/l has been suggested. Tocainide kinetics were studied in 6 healthy subjects and 16 patients with acute myocardial infarction. There was good accordance in kinetics of healthy subjects and patients. After intravenous administration the mean t1/2 was about 14 hr, volume of distribution about 3.0 l/kg, and corrected renal clearance about 140 ml/min. An average of 35% of the dose was recovered unchanged in urine. After oral administration the absorption rate was rapid relative to the elimination rate, extent of bioavailability was complete, and the apparent volume of distribution was the same as that after intravenous injection. A dose regimen of 750 mg intravenously directly followed by 800 mg orally and subsequently 400 mg 3 times daily resulted in therapeutic plasma levels within 15 min. The plasma levels remained within the therapeutic range throughout a period of observation from 48 to 168 hr.
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PMID:Tocainide kinetics after intravenous and oral administration in healthy subjects and in patients with acute myocardial infarction. 735 Nov 18

The metabolism of tocainide, an experimental antiarrhythmic drug, was studied in humans. Urinary excretion of unchanged drug was 28-55% in 24 hr after oral dosing. Urine hydrolysis with hydrochloric acid or beta-glucuronidase increased tocainide recovery to 55-79%. Saccharo-1,4-lactone inhibited the beta-glucuronidase-mediated tocainide recovery increase. Adjustment of urine to pH 13 produced a compound identified as 3-(2,6-xylyl)-5-methylhydantoin. Evidence suggests that it was derived from the same metabolite that formed the additional tocainide after acid or beta-glucuronidase treatment. Tocainide carbamoyl O-beta-D-glucuronide is the structure proposed for the metabolite. The suggested pathway for its formation involves the addition of carbon dioxide to the amino nitrogen of tocainide followed by uridine diphosphate-glucuronic acid conjugation.
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PMID:Tocainide conjugation in humans: novel biotransformation pathway for a primary amine. 735 40

In whole cell voltage clamp experiment with isolated guinea pig ventricular myocytes, tocainide was shown to exhibit a concentration-dependent inhibition of calcium current (ICa) and delayed rectifier potassium current (IK). Tocainide with a therapeutic concentration of 50 mumol.L-1 significantly inhibited the ICa and Itail (deactivating tail current of IK) by 16% and 3% respectively. Inhibition of ICa by tocainide was also shown to be dependent upon stimulating frequencies, with a greater blockade occurring at 2.0 Hz (57%) than at 0.2 Hz (17%). Tocainide was found to inhibit the IK,ATP by 74% at 200 mumol.L-1 but not at 50 mumol.L-1. These inhibitory effects on ICa and IK can probably explain the therapeutic effect of tocainide on supraventricular tachycardia, and the shortening of plateau phase of action potential.
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PMID:[Inhibitory effect of tocainide on calcium current and potassium current in guinea pig ventricular myocytes]. 757 80

We describe the case of a patient in whom a syndrome of fever, pancytopenia, pleural effusion, hepatosplenomegaly, positive ANA antibodies, and bone marrow granulomas developed in association with tocainide therapy. Tocainide, a recognized, albeit rare, cause of fever, lupus-like syndrome, and cytopenias, should be added to the list of medications that can cause bone marrow granulomas.
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PMID:Bone marrow granulomas, fever, pancytopenia, and lupus-like syndrome due to tocainide. 805 99

The effect of 5 days of oral tocainide (400 mg every 8 h) on the kinetics of theophylline given as a single 5 mg kg-1 i.v. infusion over 30 min was investigated in eight healthy male nonsmokers. Treatment with tocainide decreased the plasma clearance of theophylline from 37.5 +/- 6.9 (mean +/- s.d.) to 33.7 +/- 5.0 ml kg-1 h-1 (difference -3.8, 95% CI, -1.7 to -5.9; P = 0.004) and increased its terminal elimination half-life from 9.7 +/- 2.5 to 10.4 +/- 2.1 h (difference 0.7, 95% CI, 0.2 to 1.2; P = 0.011). Tocainide decreased the formation clearances of 3-methylxanthine and 1-methyluric acid, but the formation clearance of 1,3-dimethyluric acid was unaltered. These data indicate that tocainide exerts a modest inhibitory effect on theophylline metabolism. The magnitude of this change is substantially smaller than that reported to be produced by mexiletine.
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PMID:The effect of tocainide on theophylline metabolism. 848 25

The effects of three class I antiarrhythmic drugs procainamide, tocainide and phenytoin on undamaged myocardial mitochondrial ATPase [ATP: phosphohydrolase EC 3.6.1.3] activity were evaluated in guinea pig heart preparations. Tocainide inhibited the ATPase activity in the range of 1.0 nM-500 mM, exhibiting IC20 and IC50 values of 9.4 +/- 0.7 microM and 5.2 +/- 0.4 mM, while procainamide exhibited significant (p < 0.05) inhibitory effect only at concentrations above 1.0 mM with IC20 and IC50 values of 35.4 +/- 2.7 mM and 90.8 +/- 3.7 mM, respectively. On the other hand, phenytoin inhibited the enzyme by 17% and 8% at 1.0 nM and 1.0 microM respectively, while it stimulated it at higher concentrations, thereby increasing its activity by 10%, 57% and 227% at 10, 100, 1000 microM, respectively. The inhibitory actions of these drugs are probably related to their lipophilicity and membrane stabilizing activity, while the stimulatory effect of phenytoin suggests some specific interaction with some component(s) of the oxidative phosphorylation or respiratory chain.
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PMID:Effects of procainamide, tocainide and phenytoin on guinea pig cardiac mitochondrial ATPase activity. 848 38

Tocainide was administered to 23 cardiomyopathic Doberman Pinschers at doses of 15 to 25 mg/kg tid. These doses produced peak (2-hour) serum concentrations of 6.2 to 19.1 mg/L and trough (8-hour) serum concentrations of 2.3 to 11.1 mg/L. Anorexia and gastrointestinal disturbances occurred in 8 dogs (35%) at doses (15.6 to 25.0 mg/kg) that were not different from those (16.0 to 26.0 mg/kg) received by dogs that did not experience toxicity. Doses producing peak serum concentrations that were either greater or less than 14 mg/L were not different. Likewise, doses producing trough values that were either greater or less than 6 mg/L were not different. The mean dose that produced peak serum concentrations of 10 to 13.6 mg/L and trough concentrations of 4.2 to 10.0 mg/L was 17.9 mg/kg, and was associated with anorexia in 4 dogs. Mean peak serum concentrations associated with toxicity (14.4 mg/L) were significantly higher (P = .02) than dogs not experiencing toxicity (11.8 mg/L). Serious adverse effects occurred in 7 of 12 dogs (58%) receiving tocainide for longer than 4 consecutive months. Progressive corneal endothelial dystrophy occurred in 3 dogs. Although a causal effect could not be proven, 6 dogs experienced renal dysfunction during treatment. Drug doses in these 7 dogs were similar to those received by other dogs. At least a 70% reduction of the total numbers of ventricular premature contractions occurred in 80% of dogs treated, and ventricular tachycardia was eliminated in 90% of affected dogs by the time of the first posttreatment Holter recording. Long-term control of ventricular tachyarrhythmias was difficult to achieve in some dogs when the left ventricular shortening fraction was less than approximately 17%.
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PMID:Efficacy and toxicity of tocainide for the treatment of ventricular tachyarrhythmias in Doberman pinschers with occult cardiomyopathy. 881 48


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