Disopyramide serum and pharmacologic effect kinetics applied to the assessment of bioavailability.
1 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. 5 The 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 less than 0.005), the 5--15% difference between the two formulations should not normally be of any clinical significance.
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D004206:Disopyramide / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D004562:Electrocardiography; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D011725:Pyridines / Q000378:metabolism*; D013997:Time Factors
D011725:Pyridines; D004206:Disopyramide