Longitudinal Study of Tacrolimus in Lymphocytes During the First Year After Kidney Transplantation

Introduction: Tacrolimus (TAC) is an immunosuppressive drug used after organ transplantation. Dosing is adjusted using whole blood (WB-TAC) measurements. Patients within the therapeutic WB-TAC window still experience rejections and adverse effects. Alternative monitoring methods are therefore warranted. The authors developed a method for measuring TAC in peripheral blood mononuclear cell (PBMC) isolates (PBMC-TAC) and performed a pharmacokinetic study in a cohort of kidney transplant patients during the first year after transplantation. Methods: PBMCs were isolated from whole blood by gradient centrifugation. After methanol-based extraction, liquid chromatography with tandem mass spectrometry was used to determine TAC in the extract. PBMC-TAC was normalized to the number of cells and alternatively to the protein amount in cells. Predose and postdose (1.5 hours) samples from kidney transplant patients were collected at 1 week, 6 weeks, and 1 year after transplantation. WB-TAC was measured using immunoassay. Results: The PBMC-TAC assay fulfilled the validation criteria of the European Medicines Agency guidelines. Twenty-nine patients completed the study. Predose PBMC-TAC was (median) 23 (1 week), 33 (6 weeks), and 27 pg/106 cells (1 year). Postdose PBMC-TAC was 44, 30, and 27 pg/106 cells at 1 week, 6 weeks, and 1 year after transplantation, respectively. Predose WB-TAC (median) was 5.0, 6.0, and 5.4 mcg/L, and postdose WB-TAC was 10.5, 8.3, and 9.1 mcg/L, respectively,...
Source: Therapeutic Drug Monitoring - Category: Drugs & Pharmacology Tags: Original Article Source Type: research