[Correction model of the sampling time error on the blood trough concentration of tacrolimus in non-sustained-release dosage form for renal transplant recipients]

Abstract

Objective: To establish correction model of the sampling time error on the blood trough concentration of tacrolimus in non-sustained-release dosage form for renal transplant recipient and improve the accuracy of drug dose assessment and clinical adjustment in renal transplant recipients. Methods: Visit records of 206 outpatients in the Department of Transplantation, Nanfang Hospital, Southern Medical University were retrospectively collected from October 15, 2022 to October 30, 2022. The distribution of sampling time of tacrolimus blood drug concentration was described and the time range of correction was determined. Twenty inpatients after renal transplantation in the Department of Transplantation, Nanfang Hospital, Southern Medical University from October 1, 2022 to November 30, 2022 were prospectively included, and their demography data, laboratory test results during follow-ups, and CYP3A5 genotype were collected. The patients took tacrolimus in non-sustained-release dosage form every 12 h starting from 19∶30 on the day of admission. Peripheral blood samples were collected from the patients on the second day of admission at 7∶30 and on the third day at 6∶00-10∶00 every 30 minutes to test the blood concentration of tacrolimus. Using the collection time as the independent variable and the blood tacrolimus concentration as the dependent variable, a simple linear regression was performed to fitting a linear model of tacrolimus blood concentration-sampling time. Multiple linear regression was performed to analyze the influencing factors of the tacrolimus metabolic rate within a specific period and generate the regression equation. Results: The 206 outpatients aged (46±13) years, including 131 males (63.6%). The time gap [M (Q₁, Q₃)] between the sampling time of the follow-up outpatients and standard C₁₂ was 24 (13.0, 46.5) min, and the maximum time gap was 135 min. The 20 enrolled inpatients aged (45±12) years, including 15 males (75.0%). There was no significant difference in the blood concentration of tacrolimus collected at 7∶30 on the second (7.87±2.21)ng/ml and third days (7.84±2.33)ng/ml after admission of the enrolled inpatients (P=0.917), and the blood tacrolimus concentration rhythm was stable in the trial. The plasma concentration of C_10.5-C_14.5 was linearly related to the time, with R² [M (Q₁, Q₃)] 0.88 (0.85, 0.92) and all P<0.05. The metabolic rate of tacrolimus during C_10.5-C_14.5=0.984+0.090×basic concentration of tacrolimus (ng/ml)-0.036×body mass index+0.489×CYP3A5 genotype-0.007×hemolobin(g/L)-0.035×alanine aminotransferase (U/L)+0.143×total cholesterol (mmol/L)+0.027×total bilirubin (μmol/L), with R²=0.85. Conclusion: This study propose a correction model for tacrolimus (non-sustained-release dosage form) trough concentration around C₁₂, which is helpful for clinicians to easily and accurately assess renal transplant recipients' tacrolimus exposure.