Disposition Kinetics of Disopyramide in Human Healthy Volunteers Described by an Open Three Compartment Model

Abstract

Disposition kinetics of disopyramide was examined in an open randomised cross-over study in 8 healthy volunteers. Disopyramide was randomly administered as a single bolus injection (150 mg) over a period of 5 min. and as an infusion (28.2) mg/h to steady state. Disposition kinetics of disopyramide were most precisely described by an open three compartment model according to Akaike's information criteria. Significant positive correlations (0.909 +/- 0.04, P less than 0.05 (injection study); 0.787 +/- 0.11, P less than 0.05 (infusion study] were observed between total serum concentrations of disopyramide and renal clearance while no significant correlation could be demonstrated between free serum concentrations and renal clearance. This implies a constant value of unbound renal clearance. The results are consistent with non linear kinetics (mainly caused by the variable free fraction of the drug), when based on total serum concentrations. The disposition of unbound disopyramide, however seems to be linear (i.e. the kinetic parameters are independent of dose) in the bolus injection study. Total elimination clearance (free and total), volume of distribution and elimination half-life were significantly higher in the steady state experiment than in the bolus injection study.

Development of a novel method for predicting human volume of distribution at steady-state of basic drugs and comparative assessment with existing methods

“…The current comparative assessment was based on mean measured values of V ss compiled in the literature for each drug. Considering that the in vivo value of V ss may change from a source to another5, 26 the conclusion might differ depending of the set of in vivo values. The current correlation method and those previously developed by other authors7–9 are first attempts to predict V ss in vivo based on muscle Kpu data (and/or RBCu).…”

Disopyramide concentrations in human plasma and saliva: Comparison of disopyramide concentrations in saliva and plasma unbound concentrations

“…Although the pharmacokinetics of disopyramide in man have been studied thoroughly [6,17], the salivary excretion of the drug has not been investigated in detail, especially for the relationship with the unbound concentrations in plasma [18,19]. We have studied the disopyramide concentrations in saliva and plasma (total and unbound) samples after disopyramide (200 mg) oral dosing in six healthy male subjects.…”