DISOPYRAMIDE PHOSPHATE - TISSUE UPTAKE AND RELATIONSHIP BETWEEN DRUG CONCENTRATIONS IN PLASMA AND MYOCARDIUM OF RATS

Abstract

Tissue uptake of total-14C and disopyramide (DP) [antiarrhythmic agent] was examined in rats following 5-100 mg/kg doses of 14C-disopyramide phosphate [14C-DPP]. Disopyramide was the major 14C constituent in the plasma or tissues. Gastrointestinal absorption of 14C-DPP was 86% as determined from areas under the plasma total-14C concentration-time curves following 10 mg/kg oral or i.v. administration. Total-14C was widely distributed in tissues and at 2 h the highest uptake occurred in the fat, liver and spleen giving concentrations ranging 7-15 times that in plasma. In the thymus, adrenals, lungs, salivary glands, testes and muscle the concentrations were about twice that in plasma, in the heart and eyes similar to that in plasma, and in the brain less than 1/3 that in plasma. Uptake and elimination characteristics of total-14C or DP in plasma and myocardium were similar. The 2-h plasma or myocardium DP concentrations were linearly related to the oral dose in the 5-50 mg/kg range. In 3 days about 30% (oral) and 39% (i.v.) of the 14C dose (10 mg/kg) was excreted in the urine, 64% (oral) and 54% (i.v.) in the feces, and < 2.1% remained in the carcass. Composition of urinary and fecal metabolites was similar after oral or i.v. administration of the drug.