Disopyramide phosphate: tissue uptake and relationship between drug concentrations in the plasma and myocardium of...

Tissue uptake of total-14C and disopyramide (DP) was examined in rats following 5 to 100 mg/kg doses of [14C]-disopyramide phosphate [14C-DPP]. Disopyramide was the major 14C constituent in the plasma or tissues. The gastrointestinal absorption of [14C]-DPP was 86% as determined from the 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 hr the highest uptake occurred in the fat, liver and spleen giving concentrations ranging from 7 to 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 one-third that in plasma. The uptake and elimination characteristics of total-14C or DP in plasma and myocardium were similar. The two-hour plasma or myocardium DP concentrations were linearly related to the oral dose in the 5 to 50 mg/kg range. In three 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 less than 2.1% remained in the carcass. The composition of the urinary and fecal metabolites was similar after oral or i.v. administration of the drug.