Population Pharmacokinetics and Dosing Regimen of Lithium in Chinese Patients With Bipolar Disorder.

Background: Lithium is an effective medication approved for the treatment of bipolar disorder (BD). It has a narrow therapeutic index (TI) and requires therapeutic drug monitoring. This study aimed to conduct a population pharmacokinetics (PPK) analysis of lithium and investigate the appropriateness of the dosing regimen according to different patient characteristics. Methods: A total of 476 lithium concentrations from 268 patients with bipolar disorder were analyzed using nonlinear mixed-effects modeling. Monte Carlo simulations were employed to investigate the influence of covariates, such as weight, creatinine clearance, and daily doses of lithium concentrations, and to determine the individualized dosing regimens for patients. Results: Lithium PK was described by a one-compartment model with first-order absorption and elimination processes. The typical estimated apparent clearance was 0.909 L/h-1 with 16.4% between-subject variability in the 62 kg patients with 116 ml/min creatinine clearance and 600 mg daily doses. To achieve a target trough concentration (0.4-0.8 mmol/L) in the maintenance phase, the regimen of 500 mg than 750 mg daily dose was recommended for patients with renal insufficiency and weighing 100 kg. Conclusion: A PPK model for lithium was developed to determine the influence of patient characteristics on lithium pharmacokinetics. Weight, creatinine clearance, and total daily dose of lithium can affect the drug's clearance. These results demonstrate the nonlinear renal excretion of lithium; hence, dosage adjustments are recommended for patients with renal insufficiency.

Abnormally altered patterns of whole brain functional connectivity network of posterior cingulate cortex in remitted geriatric depression: a longitudinal study.

AIMS: A longitudinal study investigated the remitted geriatric depression (RGD) patients' persistent cognitive impairment and potential correlation with their PCC functional connectivity network. METHODS: A total of 14 RGD patients and 18 matched controls were recruited. All subjects finished the neuropsychological tests and functional magnetic resonance imaging scan at baseline and follow-up. A spherical region of interest was placed in PCC to calculate the functional connectivity, and further analysis was employed to detect correlations between longitudinal changes in the brain regions and neuropsychological data. RESULTS: There were significant cognitive declines in RGD patients at baseline and follow-up. Altered patterns of functional connectivity were detected within the RGD group showing correlations with neuropsychological tests. The longitudinal change in functional connectivity between PCC and cerebellum posterior lobe was correlated with longitudinal changes in auditory verbal memory test-recall (r=0.550, P=0.042). The longitudinal change in functional connectivity between PCC and right parahippocampal gyrus was correlated with Trail Making Test-A (r=0.631, P=0.015). The longitudinal change in functional connectivity between PCC and supramarginal_R was correlated with Mini-Mental State Examination (r=-0.630, P=0.016). CONCLUSIONS: RGD patients performed worse cognitive function, and altered PCC functional connectivity network might have a role in these cognitive declines.