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.

Although tacrolimus has been widely used in patients undergoing lung transplantation, few studies have reported the pharmacokinetics of tacrolimus in Chinese patients after lung transplantation. Thus, we aimed to investigate its pharmacokinetics and influential factors in this patient cohort in the early stage after lung transplantation. We enrolled 14 lung transplant recipients who were treated with tacrolimus and voriconazole. We then collected intensive blood samples within a 12-hour dosing interval and analysed them via liquid chromatography-mass spectrometry. The pharmacokinetic parameters of tacrolimus were calculated using non-compartmental analysis, and the influence of physio-pathological characteristics and CYP3A5*3 and CYP3A4*1G genotypes on the pharmacokinetics of tacrolimus was assessed. Using linear regression analysis, we then investigated the correlation between tacrolimus concentration at different sampling points and measured the area under the curve (AUC0 − 12h). Our results showed a mean apparent clearance (CL/F) rate of 14.2 ± 11.0 L/h, with CYP3A5*1 carriers having a CL/F rate five times higher than non-carriers (P < 0.001). Furthermore, tacrolimus concentration 4 h after the administration had the strongest correlation with AUC0 − 12h (R2 = 0.979). In summary, tacrolimus pharmacokinetics varied largely between patients during the early-stage post-lung transplantation, which could be partly explained by CYP3A5 genetic polymorphisms. Therefore, it is crucial to closely monitor tacrolimus blood concentration in the early stages after lung transplantation.