Lithium pharmacokinetics in the obese

Introduction: The purpose of this study was to investigate the disposition of lithium in obese subjects compared with the disposition in normal weight volunteers. Methods: Ten obese volunteers (weight, 110.2 ± 28.6 kg) were compared with eight evaluable normal weight volunteers (weight, 63.1 ± 6.6 kg). Oral lithium citrate (31.4 mEq) was administered and blood samples were obtained over a 48-hour period. Creatinine clearance (CL(CR)) was determined from a 12-hour urine collection. Total body water was determined by the deuterium oxide dilution method. Results: The clearance of lithium (CL(Li)) for the obese group was significantly greater than that for the control group (33.9 ± 7.0 ml/min versus 23.0 ± 6.2 ml/min; p = 0.005). The steady-state volume of distribution (V(SS)) for the obese group was significantly less than that for the control group (0.42 ± 0.09 L/kg versus 0.66 ± 0.16 L/kg; p = 0.001). For the combined group, V(SS) was significantly correlated with ideal body weight and fat free mass but not with total body weight. The CL(Li) was significantly correlated with total body weight, but not with CL(CR). Conclusions: The pharmacokinetic properties of lithium were significantly different for the obese subjects compared with those the normal weight control subjects. At steady state there is a direct proportionality between CL(Li) and the dose required to achieve a given serum lithium concentration, therefore the results of this study suggest that obese patients may require larger lithium maintenance doses than nonobese patients.