Due to its proven clinical effectiveness, lithium has been considered as a corner stone for the long-term treatment of Bipolar Disorder (BPD) for more than half a century. The objective of this study was to evaluate the effect of patients’ different co-variables on lithium pharmacokinetics and the development of a pharmacokinetic model for the estimation of lithium clearance in Egyptian bipolar patients; this model can be used afterwards during dosage adjustment to achieve target’s steady-state plasma concentrations in similar settings. The study was conducted on 65 adult Egyptian bipolar patients of both genders, in both the in- and out-patient settings in the Institute of Psychiatry, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Patients’ full profiles were prepared, containing all their data. Single daily dose regimen was followed by all patients and one blood sample was drawn 12 ± 0.5 hours post dose for steady-state lithium concentration, sodium level and serum creatinine determinations. Lithium trough levels were determined using Flame Emission Photometry technique. Data analysis and regression modeling revealed a significant correlation between total body weight (TBW), body surface area (BSA) and lithium clearance. Due to multicollinearity, BSA was excluded from the basic non-linear regression equation and TBW was found to be the only covariate affecting lithium clearance. Mean lithium clearance was found to be 0.243 ± 0.097 Lit/Kg/day, ranging from 0.091 to 0.71 Lit/Kg/day.