To investigate trough concentration of vancomycin in liver transplant recipients during hospitalization and its influencing factors, and to evaluate the value of population pharmacokinetics called software Java PK for Desktop (JPKD) in liver transplant recipients.

A retrospective analysis was conducted on the clinical data of liver transplant recipients who treated with vancomycin and received therapeutic drug monitoring in Zhongshan Hospital of Fudan University from January 2016 to December 2019. The recipients were divided into reach the standard group and fail to reach the standard group according to whether the initial steady-state trough concentration of vancomycin reached 10-20 mg/L. The influencing factors of the initial steady-state trough concentration of vancomycin in liver transplant recipients were also analyzed. For liver transplant recipients with the steady-state trough concentration and received dose adjustment, JPKD software was used to predict the trough concentration of the adjusted regimen. The weight deviation (WRES) between the predicted and the measured concentration was used to evaluate the predictive ability of JPKD software for trough concentration of vancomycin. Measurement data were compared by two independent samples t-test or Mann-Whitney U test, and enumeration data were compared by Chi-square test or Fisher′s exact test. Variables with P<0.20 were included in the binomial logistic regression model, backward LR method to analyze the influencing factors of initial steady-state trough concentrations of vancomycin. A P<0.05 was considered statistically significant.

A total of 58 liver transplant recipients were finally enrolled, 44 of them got dosing regimen adjustment of vancomycin during treatment. The initial and adjusted daily doses of vancomycin were (1.79±0.37) and (1.49±0.61) g/d, respectively, and the steady-state trough concentrations were (18±8) and (15±7) mg/L, respectively. After initial administration, the proportion of recipients with vancomycin trough levels reaching the target was 46.6% (27/58); 11 (19.0%) of the 31 recipients in the substandard group had low exposure (<10 mg/L) and 20 (34.5%) had high exposure (>20 mg/L). Logistic regression analysis revealed that vancomycin daily dose (OR=15.807, P<0.05) and serum urea nitrogen before administration (OR=1.101, P<0.05) were the independent influencing factors of initial trough concentration of vancomycin in liver transplant recipients. Among 44 liver transplant recipients who had adjusted dosing regimen during the treatment, 68.2% (30/44) achieved target trough concentration. The measured concentration and predictive concentration were (15±7) mg/L and (14±5) mg/L respectively. The proportion of liver transplant recipients with WRES ≤30% was 81.8% (36/44).

The proportion of vancomycin initial trough concentration reaching the target needs to be improved in perioperative liver transplant recipients. As the influencing factors of initial trough concentration, vancomycin daily dose and serum urea nitrogen before administration should be paid more attention. JPKD software has a good predictive ability to liver transplant recipients′ vancomycin trough concentration, and may be used to assist clinicians in developing individualized drug protocols.