Role of concentration-dependent plasma protein binding in disopyramide disposition

Plasma binding of disopyramide.

“…MOULD, G. & DOLLERY, C.T. (1979 (Ward & Kinghorn, 1976) and non-linear behaviour has been reported, with some authors maintaining that dose-dependency can be explained by variations in plasma protein binding (Hinderling & Garrett, 1976;Meffin, Robert, Winkle, Harapat, Peters & Harrison, 1979), while others consider this aspect to be insufficient to explain the evidence (Cunningham, Shen, Shudo & Azarnoff, 1977Ilett, Madsen & Woods, 1979). Adding to the difficulty of answering the latter feature, there may be considerable variation in the extent of plasma binding between patients (Meffin et al, 1979).…”

“…Steinhardt & Reynolds (1969) have described the problems with this approach and have stated that the only reliable way of assuring true equilibrium is to obtain the same bound and free drug concentrations when the drug is initially placed on either side. Meffin et al (1979) have stated that there is large inter-patient variability of disopyramide binding in patients with cardiac disease. Our results do not support this contention in healthy volunteers; indeed, for a biological phenomenon, there is surprising conformity (Figure 3) Myocardial infarction appears to decrease disopyramide binding in the therapeutic range, but this would not have been inferred when comparing the data of Meffin et al (1979) with previous workers (Figure 3).…”

“…Meffin et al (1979) have stated that there is large inter-patient variability of disopyramide binding in patients with cardiac disease. Our results do not support this contention in healthy volunteers; indeed, for a biological phenomenon, there is surprising conformity (Figure 3) Myocardial infarction appears to decrease disopyramide binding in the therapeutic range, but this would not have been inferred when comparing the data of Meffin et al (1979) with previous workers (Figure 3). Decreased binding might be expected in view of the well known decrease in plasma albumin concentrations after infarction (Johansson, Kindmark, Trell & Wollheim, 1972;Smith, Bos, Esseveld, Van Eijk & Gerbrandy, 1977), and the finding by Chien, Lambert & Karim (1974) …”

Calculation of drug concentration in plasma after equilibrium dialysis.

“…One side of the cell contained isotonic Krebs Ringers bicarbonate buffer (pH 7.4) with various concentrations of unlabelled disopyramide (range 0 to 9.25 ,ug/ml) and 0. (Meffin et al, 1979;Wilding et al, 1977). However, for the reasons presented here, we feel that the specific activity method can be used to accurately calculate CPequ and is as valid as measuring CPequ by conventional analytical methods, but simpler and less prone to analytical error than the latter.…”

Dihydroquinidine versus disopyramide: Efficacy in patients with chronic stable ventricular ectopy

“…Each sample was assayed in duplicate and the mean value was utilized to construct plasma-level response curves. The pharmacokinetic characteristics of DQ were determined in a previous study (Regazzi-Bonora et al, 1982) while those of D were taken from the literature (Hulting and Jansson, 1977;Meffin et al, 1979). …”