Disopyramide: Serum level and arrhythmia conversion

Niarchos, Andreas P.

doi:10.1016/s0002-8703(76)80403-6

Cited by 100 publications

(45 citation statements)

References 12 publications

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“…The previous paper (10) and the present results indicate that the steady state and non-steady state effects on seen at 50 W disopyramide were qualitatively similar to and were simply more pronounced than the effects seen at 20 /cM disopyramide which roughly cor responded to the maximum effective (anti arrhythmic) plasma concentration (12,13).…”

Section: Discussionsupporting

confidence: 85%

“…After an equilibration period of at least one hour, the transmembrane potential was recorded by means of a conventional microelectrode filled with 3 M KCI (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) The recovery process of Vmy, was examined in the following two ways: (i) the process within the basic stimulation interval of 1 sec (premature recovery) was studied by intro ducing premature test stimuli (2-3 times the intensity of the basic stimulus) in every 8-10 basic stimuli, (ii) the process beyond the basic stimulation interval (post-interruption recovery) was studied by assessing in the first response after interruption of the basic stimuli for various periods (2 sec to 10 min). The term "diastolic interval" is defined as the interval from the 90% repolarization time of the conditioning action potential to the onset of the test action potential.…”

Section: Methodsmentioning

confidence: 99%

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Effects of disopyramide on the maximum rate of rise of action potential (Vmax) in guinea-pig papillary muscles.

1982

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Abstract-The correlation between the steady state and non-steady state depression of Vn,;,,; by 50 /LM disopyramide was investigated in 2.7, 5.4 and 8.1 mM [K+],, using isolated guinea-pig papillary muscles. An elevation of [K+],, from 2.7 to 8.1 mM strengthened the depressant action of the drug on Vma, (steady state) at 1 to 5 Hz, but attenuated this action at 0.05 and 0.1 Hz. The Vmax-membrane potential (Vm) relationship (steady state) was examined at stimulation rates of 0.

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Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Effects of disopyramide on the maximum rate of rise of action potential (Vmax) in guinea-pig papillary muscles.

1982

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“…Bearing in mind the relatively wide therapeutic ratio associated with this drug-effective serum levels range from 2.8 to 7.5 g.g/ml (Niarchos, 1976 dose interval When this formula is applied to subject CC, where the difference between the two preparations was most marked, it is at once obvious that these differences are reflected by only small changes in steady state serum concentrations. A dose of 400 mg daily would result in serum concentrations of 3.0 gg/ml with Rythmodan and 4.0,g/ml with Norpace.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it has been used successfully in the treatment of a variety of arrhythmias (Hirtel, Louhija & Konttinen, 1974;Mizgala & Huvelle, 1976;Niarchos, 1976). It acts principally by slowing conduction in the His-Purkinje system and by increasing the effective refractory period of the atria and ventricles (Spurrell, Thorburn, Camm, Sowton & Deuchar, 1975).…”

Section: Disopyramidementioning

confidence: 99%

Disopyramide serum and pharmacologic effect kinetics applied to the assessment of bioavailability.

Bryson¹,

Whiting²,

Lawrence³

1978

Brit J Clinical Pharma

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I Serum, urine and pharmacologic effect (prolongation of the QT interval) kinetics of the antiarrhythmic disopyramide have been investigated in eight volunteers after intravenous administration (2 mg/kg) and oral administration (300 mg) of the two commercially available preparations, Rythmodan (Roussel Laboratories) and Norpace (Searle Laboratories). 2 An open one compartment body model adequately described the kinetics of disopyramide in serum and urine. 3 After intravenous administration, the following average pharmacokinetic parameters were found: biological half-life, 7.8 h; total clearance, 95 ml/min; renal clearance, 54 ml/min; apparent volume of distribution, 60 litres. 4 After oral Rythmodan and Norpace, serum concentration profiles and urinary excretion data revealed significant differences in rates of absorption, times required to achieve peak serum concentrations and biological half-lives. These differences were largely due to the relatively slow absorption characteristics of Norpace. SThe absence of hysteresis in plots of QT prolongation against disopyramide serum concentration after oral administration indicated that serum and pharmacologic effect kinetics were indistinguishable within a kinetically equivalent compartment. 6 Analysis of both serum and urine data showed that while Norpace had a significantly higher degree of bioavailability (P< 0.005), the 5-15% difference between the two formulations should not normally be of any clinical significance.

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“…For example, remarkably little is known of the effects of smoking on the pharmacokinetics and/or metabolism of most important cardiovascular drugs, many of which exhibit steep serum concentration-response relationships (Niarchos, 1976;Huang & 0ie, 1982) Water intake was approximately 250 ml hourly during the first 3 h of the study.…”

mentioning

confidence: 99%

Disopyramide pharmacokinetics and metabolism: effect of inducers.

Kapil

Axelson

Mansfield

et al. 1987

Brit J Clinical Pharma

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1. The disposition of orally administered disopyramide was studied in a population of smokers (n = 6) and non‐smokers (n = 8) before and during phenobarbitone treatment (100 mg daily for 21 days; Cp 21st day = 13.9 +/− 2.0 micrograms ml‐1). The comparative inducibility of these populations by phenobarbitone was assessed as was the inductive effect of cigarette smoking, per se. Furthermore, the determinants of the intensity of the inductive effect were examined, as well as the effect of the barbiturate on the binding of disopyramide to alpha 1‐acid glycoprotein (AGP). 2. Smokers and non‐smokers exhibited similar half‐ lives (6.48 +/− 1.49 vs 6.66 +/− 1.02 h), apparent total body clearances (0.100 +/− 0.020 vs 0.117 +/− 0.034 l h‐1 kg‐1), mean renal clearances (0.043 +/− 0.0093 vs 0.057 +/− 0.013 l h‐1 kg‐1) and apparent intrinsic metabolic clearances (0.057 +/− 0.015 vs 0.060 +/− 0.024 l h‐1 kg‐1) before phenobarbitone treatment. 3. Both populations responded comparably to barbiturate exposure in that apparent intrinsic metabolic clearance more than doubled. Interestingly, the magnitude of this increase was highly dependent on the observed baseline apparent intrinsic metabolic clearance, (r' = 0.81; P less than 0.001). 4. Phenobarbitone treatment of non‐smokers resulted in an increase in the AUC of the active metabolite N‐despropyl disopyramide (MND), but not significantly (3.8 +/− 1.6 vs 4.1 +/− 2.3 micrograms ml‐1 h). Similar results were observed in smokers (3.5 +/− 1.4 vs 3.9 +/− 2.0 micrograms ml‐1 h, respectively). 5. The percent of administered dose recovered in urine as disopyramide in non‐smokers was significantly decreased upon phenobarbitone treatment (43 +/− 6% vs 25 +/− 5%), whereas the percent of dose recovered as MND increased significantly in this group (25 +/− 6% vs 31 +/− 5%). The population of smokers responded similarly. 6. At doses typically used to achieve hepatic microsomal enzyme induction in man, phenobarbitone treatment caused no significant change or trend towards a change in serum AGP concentrations as measured using the radial immunodiffusion method in nonsmokers (67.4 +/− 19.9 mg dl‐1 vs 68.0 +/− 40.7 mg dl‐1) or smokers (64.5 +/− 15.7 vs 67.9 +/− 14.9). Similarly, when AGP concentration was estimated in serum from non‐ smokers using a nephelometric method no effect attributable to phenobarbitone was observed (47.9 +/− 1.3 vs 47.9 +/− 16.8 mg dl‐1). Consistent with this observation, disopyramide free fraction was not affected by barbiturate treatment.

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Disopyramide: Serum level and arrhythmia conversion

Cited by 100 publications

References 12 publications

Effects of disopyramide on the maximum rate of rise of action potential (Vmax) in guinea-pig papillary muscles.

Effects of disopyramide on the maximum rate of rise of action potential (Vmax) in guinea-pig papillary muscles.

Disopyramide serum and pharmacologic effect kinetics applied to the assessment of bioavailability.

Disopyramide pharmacokinetics and metabolism: effect of inducers.

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