Pharmacokinetics of tocainide in patients with renal dysfunction and during haemodialysis

Wiegers, U.; Hanrath, P; Kuck, K. H.; Pottage, A.; Graffner, Christina; Augustin, J.; Runge, Martin

doi:10.1007/bf00609893

Cited by 37 publications

(2 citation statements)

References 8 publications

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“…'7-26 In animals, including dogs, tocainide raises the ventricular fibrillation threshold. [17][18][19][20][21][22][23][24][25][26] Peak plasma concentrations of tocainide occurred in approximately 2 hours in the dogs in this report. Therapeutic plasma concentrations in humans are 4 to 10 mg/L, with a preferred range of 6 to 10 mg/L.17 There is an overlap between the therapeutic range and the plasma concentrations associated with adverse effects in humans.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Toxicity of Tocainide for the Treatment of Ventricular Tachyarrhythmias in Doberman Pinschers With Occult Cardiomyopathy

Calvert

Pickus

Jacobs

1996

Veterinary Internal Medicne

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Tocainide was administered t o 23 cardiomyopathic Doberman Pinschers at doses of 15 t o 25 rnglkg tid. These doses produced peak (2-hour) serum concentrations of 6.2 t o 19.1 mg/L and trough (&hour) serum concentrations of 2.3 t o 11.1 mg/L. Anorexia and gastrointestinal disturbances occurred in 8 dogs (35%) at doses (15.6 t o 25.0 mg/kg) that were not different from those (16.0 t o 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 t o 13.6 mg/L and trough concentrations of 4.2 t o 10.0 mg/L was 17.9 mglkg, 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 ocainide is an orally administered lidocaine analog that T is indicated for the treatment of severe, potentially lifethreatening ventricular tachyarrhythmias (VTA). In humans, tocainide has been proven effective in treating symptomatic VTA in some patients unresponsive to other antiarrhythmic drugs.'-3 At recommended doses and serum concentrations, tocainide causes little hemodynamic ~h a n g e .~.~ The recommended therapeutic plasma concentration range is 4 to 10 mg/L, although a trough value of 6 mg/L is referr red.^.^ Cardiomyopathy in Doberman Pinschers is a chronic, slowly progressive disease characterized by VTA of variable seventy, sudden death, or end-stage congestive heart failre.^-'* Early in the disease, ventricular tachyarrhythmias usually are not severe, but by 1.5 to 2 years after their onset and the detection of early echocardiographic abnormalities, the VTA often become severe and this exacerbation is associated with significant reductions of ejection fra~tion.~.~"' The prevalence of sudden death in Dobermans with cardiomyopathy is approximately 20% to 30%.9.'0 Tocainide is a relatively recent addition to the antiarrhythmic group of drugs available for treating VTA. The purpose of this report is to describe doses, toxicity, and efficacy of tocainide in occult cardiomyopathy of Doberman Pinschers. MethodsFrom June 1986 through May 1990,23 Doberman Pinschers ranging in age from 1 to 11 years (mean, 8.0 yrs) that had occult cardiomyopathy and VTA were treated with tocainide. Tocainide was administered because of one or more of the following: VTA (13 dogs), a history of syncope attributable to VTA (5 dogs), and to determine drug efficacy (9 dogs). Two dogs received 2 separate courses of therapy. In all instances, arrhythmia quantification was accompllished by 24-hour ambulatory EKG (Holter) recordings.We defined occult cardiomyopathy as echocardiographic abnormalities and VTA in dogs without overt evidence of congestive heart failure (CHF); the diagnosis was based on cardiac ultrasound measurements and long-term ambulatory EKG (Holter) record...

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Section: Discussionmentioning

confidence: 99%

Efficacy and Toxicity of Tocainide for the Treatment of Ventricular Tachyarrhythmias in Doberman Pinschers With Occult Cardiomyopathy

Calvert

Pickus

Jacobs

1996

Veterinary Internal Medicne

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“…A prolongation of half-life (19.1 hours) was found by Klein et al [43] in patients recovering from acute MI (200 mg to 600 mg PO at 8-hour intervals for 2 days). It should be noted that when the renal function is impaired, the tocainide half-life is prolonged (19.2 hours), as evidenced in patients with renal dysfunction (creatinine clearance, 10-55 ml/min) [44]. It should be noted that when the renal function is impaired, the tocainide half-life is prolonged (19.2 hours), as evidenced in patients with renal dysfunction (creatinine clearance, 10-55 ml/min) [44].…”

Section: Tocainidementioning

confidence: 99%

Effects of cardiovascular disease on pharmacokinetics

Rodighiero

1989

Cardiovasc Drug Ther

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The pathophysiologic changes occurring in cardiovascular disease can affect the kinetics of drugs in several different ways. The present review examines these modifications and the underlying mechanisms. The kinetics of specific agents, such as antiarrhythmic, antihypertensive, cardiotonic, and other drugs are considered, and the clinical implications are outlined. The clinician should be aware of these modifications, because they require an adjustment of the dosage regimen. A rational basis for a correct therapeutic choice can be provided by adequate knowledge of these modifications.

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Pharmacokinetics of Cibenzoline in Patients With Renal Impairment

Canal

Flouvat

Aubert³

et al. 1985

The Journal of Clinical Pharma

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Pharmacokinetic values of cibenzoline, a new, investigational, antiarrhythmic drug, were determined in 13 patients with varying degree of renal impairment, creatinine clearance range between 5 and 53 mL/min. Cibenzoline plasma levels were measured after direct intravenous injection of one single 1 mg/kg dose. The apparent volume of distribution of the drug (276 1) was similar to that reported in healthy subjects. Total body clearance decreased with creatinine clearance, and there was a close correlation between cibenzoline renal clearance and creatinine clearance (r = 0.956; P less than 0.001). Plasma elimination half-life was prolonged, with values ranging from 7:4 to 23.6 hours. This study showed that cibenzoline total body clearance correlated with the degree of renal impairment, and it is suggested that in patients with chronic renal failure dosage should be adjusted according to creatinine clearance values.

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Pharmacokinetics of tocainide in patients with renal dysfunction and during haemodialysis

Cited by 37 publications

References 8 publications

Efficacy and Toxicity of Tocainide for the Treatment of Ventricular Tachyarrhythmias in Doberman Pinschers With Occult Cardiomyopathy

Efficacy and Toxicity of Tocainide for the Treatment of Ventricular Tachyarrhythmias in Doberman Pinschers With Occult Cardiomyopathy

Effects of cardiovascular disease on pharmacokinetics

Pharmacokinetics of Cibenzoline in Patients With Renal Impairment

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