Accuracy of the pepin method to determine appropriate lithium dosages in healthy volunteers

Objective: To assess if the lithium dosage prescribed according to the Pepin method leads to therapeutic serum concentrations of lithium. Methods: For 13 healthy volunteers, the initial daily doses of lithium were calculated according to the Pepin formula with a view to obtaining a serum lithium level of 0.8 mmol/L. Lithium was administered twice daily for 21 days, and blood samples were drawn daily, 12 hours after the last dose was taken. Dosage was adjusted if serum concentrations were below 0.6 mmol/L or above 1.0 mmol/L or if major side effects were reported. Results: Daily lithium doses ranged from 1050 mg to 1950 mg (mean 1569 mg, standard deviation [SD] 291 mg). The mean serum lithium concentrations for weeks 1, 2 and 3 were 0.74 mmol/L (SD 0.19 mmol/L), 0.67 mmol/L (SD 0.22 mmol/L) and 0.69 mmol/L (SD 0.13 mmol/L), respectively. Within-subject variance was negligible. Sixty-eight percent of the serum lithium concentration measurements fell between 0.57 mmol/L and 0.83 mmol/L, and 84% fell within the recommended therapeutic range of 0.60 mmol/L and 1.20 mmol/L. Conclusions: The Pepin method is a safe but conservative method for predicting the appropriate daily dose of lithium.