Pharmacokinetics of disopyramide in patients with imminent to moderate cardiac failure

Abstract

The parmacokinetics of disopyramide (DP) in 10 patients with imminent to moderate cardiac failure has been studied and compared with the results in normal volunteers. The biological half life of rapid distribution (T1/2 alpha) and of elimination (T1/2 beta) were increased (11.1 +/- 4.4 min and 9.7 +/- 4.2 h, respectively). Total body clearance (Clt) was decreased (0.467 +/- 0.215 ml . min-1 . kg-1), and the volume of distribution (Vd) was slightly reduced (0.610 +/- 0.1361 . kg-1), probably due to the lower cardiac index. After oral administration, the time of peak serum concentration was increased (139 +/- 89 min), and the mean peak serum concentration (2.4 +/- 0.8% dose . 1-1) was also higher than reported in normal subjects. Comparison of the areas under the concentration versus time curves after intravenous and oral administration (AUC i. v. and AUC oral) showed that DP was almost completely absorbed, its bioavailability being 97.5 +/- 15.0%.

Unchanged Absorption of Digoxin Tablets in Patients with Cardiac Failure

“…The brand of tablet used, how ever, is relatively well absorbed and an in fluence of cardiac failure upon poorly ab sorbed tablets remains possible [20,21], Our findings confirm the conclusion of previous studies with patients in right-ven tricular failure and extend it to patients in left-ventricular failure [13], Other recent pharmacokinetic studies of digoxin in heart failure [22,23] do not include administration of both oral and intravenous doses which is necessary for estimates of the extent of avail ability. An unaltered extent of availability in cardiac failure has also been reported for quinidine solution and disopyramide and furosemide tablets [24][25][26][27], Although the extent of availability was unaffected by cardiac failure, the individual values ranged from 0.40 to 0.90. This large interindividual variability could not be ex plained by other patient characteristics like renal function or age in our patients.…”

Sustained release disopyramide compared to plain capsules after change‐ over from intravenous infusion.

“…In the unstable acute phase of myocardial infarction the renal function may fluctuate, and the pharmacokinetics of disopyramide are probably also otherwise affected (Bryson et al, 1982;Ilett et al, 1979;Landmark et al, 1981). Changes in binding to acute phase proteins of a basic drug like disopyramide (Piafsky et al, 1975;Lima et al, 1981) is a possible source of error in the interpretation of the total concentration and the pharmacokinetic data.…”

“…Unfortunately, calculation of the dose is complicated by the altered disposition of disopyramide in myocardial infarction and heart failure (Bryson et al, 1982;Ilett et al, 1979;Landmark et al, 1981). In the acutely ill patient who often has delayed gastric emptying due to nausea or the effect of strong analgesics (Nimmo, 1976), oral medication may be unreliable (Kumana etal., 1982;Weissberg etal., 1982).…”

Disopyramide Plasma Concentrations Following Single and Multiple Doses of the Immediate- and Controlled-Release Capsules

“…These findings also indicated less variable absorption of disopyramide from the CR capsules. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) to detect a 20% difference in these AUCss values was 99% at a of 0.05. Using each subject as his own control, the mean bioavailability of disopyramide from the CR capsule was 96.5% of the IR capsule with 95% confidence limits of 88.2 to 104.8%.…”

“…Disopyramide pharmacokinetics are altered in patients with severe renal impairment, 6-8 acute myocardial infarction,9 -12 and cardiac failure. 13 Plasma concentrations of disopyramide are related to antiarrhythmic activity 14-17 and in the majority of patients the therapeutic plasma concentrations of disopyramide base range between 2 and 4 mcg/ml. These concentrations are generally maintained with 100 to 150 mg q6h dosing with the immediate-release (IR) capsule formulation.…”