Comparison of lithium concentrations in red blood cells and plasma in samples collected for TDM, acute toxicity, or acute-on-chronic toxicity

Background. Lithium salts (Li+) are still one of the most appropriate treatments in manic-depressive disorders. Since Li+ has a narrow therapeutic index, plasma levels must be closely monitored to verify maintenance pharmacotherapy, to prevent side effects, to evaluate compliance and to avoid increasing rates of relapse. Although it has been reported that Li+ concentrations in red blood cells (RBC) should be a better indicator of brain levels, therapeutic drug monitoring (TDM) of Li+ is not based on its routine assessment. Objective: The aim of this retrospective study was to compare Li+ concentrations in RBC and plasma and the calculated ratio (LiR = RBC/plasma concentrations) in the three groups of patients. Methods: During the past 3 years, 309 Li+ measures were collected corresponding to 165 patients classified into three subgroups (TDM, acute or acute-on-chronic intoxication). Li+ plasma (Cplasma) and RBC (CRBC) concentrations were determined by atomic absorption spectrophotometry. Results: Results showed that Li+ concentrations in plasma are significantly correlated to Li+ concentration in RBC (r = 0.81, P < 0.0001). Although a wide inter- and intra-variability was found, Cplasma, CRBC and LiR were statistically different in the three groups. Compared with TDM, Cplasma was more elevated in cases of acute intoxication whereas Li+ accumulated preferentially in RBC in cases of acute-on-chronic intoxication. Conclusion: This study shows the interest of determining Li+ in RBC and plasma for TDM, and that LiR could be a sensitive marker of intoxication and of Li+ impregnation.