Effect of body build on the clearance of atracurium: implication for drug dosing

To determine factors that influenced the clearance (Cl) of atracurium, 80 adult patients of varying body build were given an atracurium infusion according to a predetermined profile, which was scaled by lean body mass (LBM). Cl was estimated at 50-60 min by the constant infusion rate required to maintain the steady-state plasma concentrations. The efficacy of scaling the absolute Cl estimate by body build variables, in which the absolute Cl estimate is divided by the body build variable to achieve similar scaled estimates in all patients, was assessed by the bias and precision of the individual scaled Cl estimates to those in patients with a "normal" body build (23%-27% body fat). The efficacy of scaling the dose of atracurium by differing body build variables to achieve similar plasma concentrations was also assessed by bias and precision, in which the plasma concentrations from an infusion scaled by other body build variables were generated by linear simulation. Body size, as quantified by LBM, total body mass (TBW), height, and body surface area, had a significant influence on Cl, with the effect best described by LBM (respective R2, 0.487, 0.368, 0.265, 0.445). No other factors could be identified, including blood pH, serum creatinine, and drugs given during the peroperative period. The efficacy of scaling Cl by TBW (absolute Cl estimate divided by patient TBW) to achieve similar estimates in all patients was poor; Cl.TBW estimates varied inversely with patient body fat content and resulted in obese patients having smaller estimates, a mean bias of -29%, compared with those in patients with a normal body build (P = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)