Plasma binding of disopyramide.

David, BM; Madsen, BW; Ilett, K. F.

doi:10.1111/j.1365-2125.1980.tb01090.x

Cited by 24 publications

(14 citation statements)

References 15 publications

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“…At therapeutic drug concentrations the drug exhibits concentration dependent plasma binding (Hinderling et al, 1974;Cunningham et al, 1977Cunningham et al, , 1978Meffin et al, 1979;David et al, 1980). Disopyramide clearance is dependent upon the drug free fraction rather than total drug concentrations (Hinderling & Garrett 1976;Cunningham et al, 1977Cunningham et al, , 1978Meffin et al, 1979;Bryson et al, 1982b).…”

Section: Introductionmentioning

confidence: 99%

Prolonged variability in plasma protein binding of disopyramide after acute myocardial infarction.

David¹,

Ilett²,

Whitford³

et al. 1983

Brit J Clinical Pharma

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1 Disopyramide plasma binding was determined in vitro in plasma from 20 patients with acute myocardial infarction (aged 35-79 years) and in 20 age and sex matched healthy subjects. Plasma samples were collected on days 1, 5 and 12 after infarction and when the patient returned to the outpatient clinic. 2 In healthy subjects there was a significant negative correlation between disopyramide free fraction and plasma a,-acid glycoprotein (AAG) concentration. A similar correlation was observed in the patients with myocardial infarction, however this correlation was dependent on time elapsed after infarction. Disopyramide free fraction did not correlate with albumin concentration in either group. 3 Mean plasma AAG concentrations were increased by'63% within 5 days after infarction and had returned to initial levels some months later (73.5 + 7.8 days). On each of the four sampling days, a two to four fold individual variability in plasma AAG concentrations was observed. 4 Maximum increases in disopyramide plasma binding were shown on days 5 and 12 after infarction. These increases were dependent on both drug and AAG concentrations. Increases in fraction bound were greater at the higher drug concentrations. Within the usual therapeutic plasma range for disopyramide (2 to 5 mg/I), the mean increases in fraction bound, compared to day 1 data, varied from 22 to 45% respectively. 5 Sequential alteration in AAG concentration after infarction indicates that disopyramide plasma binding may not reach a'steady state until some months after infarction. Prediction of the time to achieve this steady state would be difficult due to inter-and intra-patient variability in binding.

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Section: Introductionmentioning

confidence: 99%

Prolonged variability in plasma protein binding of disopyramide after acute myocardial infarction.

David¹,

Ilett²,

Whitford³

et al. 1983

Brit J Clinical Pharma

Self Cite

View full text Add to dashboard Cite

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“…Blood samples were obtained by venepuncture and plasma was separated by centrifugation. The binding was studied at a single disopyramide concentration as the drug shows concentration-dependent binding over its therapeutic range (Cunningham etal., 1977;Karim et al, 1978;Meffin et al, 1979;David et al, 1980 Preliminary analysis showed that sex differences were in general of low importance relative to differences between age groups. In healthy adults (group 4), however, females had lower mean scores on all variables (Blain et al, 1981;Piafsky & Borga, 1977).…”

Section: Effect Of Age and Plasma Concentrations Of Albumin And A I-amentioning

confidence: 99%

Effect of age and plasma concentrations of albumin and alpha 1‐acid glycoprotein on protein binding of disopyramide.

Holt¹,

Am²,

Healey³

1983

Brit J Clinical Pharma

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“…However, both studies show that the concentration of DP cannot be used to predict that of MND in plasma, and the need for concomitant determination of both should be thoroughly considered. Concentration dependent plasma protein binding and interindividual binding variations for DP are reported by a number of authors (Chien et al, 1974, Hinderling et al, 1974Cunningham et al, 1977;Meffin et al, 1979;David et al, 1980;Aitio, 1981;Johnston & Hamer, 1982). Very little is known about the main metabolite MND which also possesses some antiarrhythmic and electrophysiological activity (for review, see Koch-Weser, 1979;Brown & Shand, 1982).…”

Section: Discussionmentioning

confidence: 99%

“…The value of measuring total plasma concentrations of DP can be further questioned by the fact that its plasma protein binding shows a wide intersubject and concentration dependent variability already within the assumed therapeutic range (Meffin et al, 1979;David et al, 1980;Lima et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Plasma binding of disopyramide and mono‐N‐dealkyldisopyramide.

Bredesen¹,

Pike²,

Lunde³

1982

Brit J Clinical Pharma

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1 Measuring total plasma levels of disopyramide (DP) and the main metabolite mono‐N‐dealkyldisopyramide (MND) in patients on maintenance therapy with DP has shown concentrations of MND comparable with those of DP, with wide intersubject variations. 2 A method which permits simultaneous measurement of unbound fraction of DP and MND has been developed. 3 In healthy subjects the unbound fraction of both DP and MND was concentration dependent, i.e. increased with higher concentrations of DP or MND. 4 The plasma protein binding of DP is altered by varying concentrations of MND. Clinically relevant concentrations of MND may increase the unbound fraction of DP approximately twofold. 5 The plasma protein binding of MND is also altered by varying concentrations of DP. Variation in the concentration of DP from the lower to the upper part of the therapeutic range may cause a 1.5‐fold increase in the unbound fraction of MND. 6 In the assumed therapeutic range of 6‐15 mumol DP/L, the interpatient variance of unbound DP concentration might be ten‐fold or even higher. The present findings indicate the need for monitoring unbound drug concentrations in any attempt to establish plasma concentration/effect relationship.

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Plasma binding of disopyramide.

Cited by 24 publications

References 15 publications

Prolonged variability in plasma protein binding of disopyramide after acute myocardial infarction.

Prolonged variability in plasma protein binding of disopyramide after acute myocardial infarction.

Effect of age and plasma concentrations of albumin and alpha 1‐acid glycoprotein on protein binding of disopyramide.

Plasma binding of disopyramide and mono‐N‐dealkyldisopyramide.

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