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- Title
Bayesian optimization of tacrolimus exposure in stable kidney transplant patients.
- Authors
Nguyen, Thomas D.; Smith, Nicholas M.; Attwood, Kris; Gundroo, Aijaz; Chang, Shirley; Yonis, Mahfuz; Murray, Brian; Tornatore, Kathleen M.
- Abstract
Study Objective: The objective was to compare tacrolimus AUC0‐12 determined by Non‐Compartmental Analysis (NCA) using intensive sampling to Maximum a Posteriori‐Bayesian (MAP‐Bayesian) estimates from robust (n = 9 samples/subject) and sparse (n = 2 samples/subject) sampling in 67 stable KTRs and a validation group of similar patients. Design: This open‐label, prospective, single center 12‐h PK study included nine serial samples collected in KTRs to determine steady‐state NCA tacrolimus AUC0‐12. Setting: This study was conducted at a single site within a large, urban hospital in the western New York area. Patients: This study described tacrolimus pharmacokinetics in stable kidney transplant recipients on maintenance tacrolimus therapy. Intervention: Robust and sparse AUC0‐12 estimates by a MAP‐Bayesian approach were obtained using the Advanced Dosing Solutions (AdDS) and ADAPT5 freeware. Limited sampling strategies were evaluated using the original population PK model (n = 67), which was also assessed using a validation group (n = 15). AUC0‐12 agreement was tested by paired t‐tests with intraclass correlation coefficient (ICC) and Bland Altman analysis. Measurements and Main Results: A total of 35 Black and 32 White stable KTRs (estimated glomerular filtration rate [eGFR] = 55.2 ± 15.7 mL/min/1.73m2) received the tacrolimus dose of 3.4 ± 1.7 mg/study with troughs of 6.8 ± 1.8 ng/mL. The NCA‐AUC0‐12 was 123.8 ± 33.6 μg·h/L compared to MAP‐Bayesian estimates for Robust‐AUC0‐12 of 124.7 ± 33.3 μg·h/L and optimal 2‐specimen Sparse‐AUC0‐12 of 119.7 ± 32.7 μg·h/L for the training group. Comparison of Robust‐AUC0‐12 to NCA‐AUC0‐12 had an ICC of 0.96 (p = 0.99) while comparison of Robust‐AUC0‐12 to Sparse‐AUC0‐12 using Pre‐dose trough [C(t0h)] and 1 h [C(t1h)] resulted in an ICC of 0.93 (p = 0.014). In the validation group, 5 Black and 10 White KTRs (eGFR = 56.4 ± 16.8 mL/min/1.73m2) received a mean tacrolimus dose of 1.9 ± 1.2 mg/study with a trough of 6.0 ± 1.7 ng/mL. The validation group's NCA‐AUC0‐12 (88.4 ± 33.1 μg·h/L) was comparable to Robust‐AUC0‐12 (85.1 ± 33.8 μg·h/L, ICC = 0.93; p = 0.12) and Sparse‐AUC0‐12 determined from C(t0h) and C(t4h) (86.7 ± 33.9 μg·h/L, ICC = 0.91; p = 0.61). Conclusion: MAP‐Bayesian estimation for patient‐specific AUC0‐12 using sparse, two‐specimen sampling is comparable to NCA and may enhance tacrolimus TDM in stable KTRs.
- Subjects
NEW York (State); KIDNEY transplantation; TACROLIMUS; URBAN hospitals; INTRACLASS correlation; GLOMERULAR filtration rate; KIDNEYS
- Publication
Pharmacotherapy, 2023, Vol 43, Issue 10, p1032
- ISSN
0277-0008
- Publication type
Article
- DOI
10.1002/phar.2848