Procainamide disposition in obesity

The pharmacokinetics of intravenous procainamide (PA) were studied in seven obese and seven normal subjects. Serum concentrations and urinary excretion rates of PA and its active metabolite, NAPA, were measured by high performance liquid chromatography. Pharmacokinetic parameters were related to ideal body weight (IBW) and total body weight (TBW). The volume of distribution at steady state (Vssd) was similar for both groups when based per unit of IBW. Plasma clearance of PA, corrected for body surface area, was greater in obese subjects when adjusted for IBW, but similar on the basis of TBW. For its components, metabolic and renal clearance, the obese subjects showed similar metabolic clearances, but a significant increase was found in renal clearance per unit of body surface area based on both IBW (normal mean, 11.9 L/h/m2; obese, 19.0 L/h/m2) and TBW (normal mean, 11.7 L/h/m2; obese, 15.7 L/h/m2). This appears to be due to increased tubular secretion of PA in the obese group. In contrast, these subjects had lower renal clearances of NAPA. Variability in disposition of PA may, thus, be affected by patient physiology and method of parameter normalization.