Tacrolimus Population Pharmacokinetic Model in Chinese Patients with
Nephrotic Syndrome and Dosing Regimen Identification Using Monte Carlo
Simulations
Abstract
Aim: The study aimed to establish a population pharmacokinetic (PPK)
model for Chinese patients with nephrotic syndrome using the patient
genotype and Wuzhi capsule dose as the main test factors. Methods: Adult
patients with nephrotic syndrome receiving tacrolimus treatment were
enrolled. A nonlinear mixed effects model was used to determine the
influencing factors of inter-individual tacrolimus metabolism variation
and establish a PPK model. To optimize the tacrolimus dosage, 10000
Monte Carlo simulations were performed. Results: The typical population
tacrolimus clearance (CL/F) value was 16.9 L/h. Increased Wuzhi capsule
and albumin doses both decreased the tacrolimus CL/F. In CYP3A5
homozygous mutation carriers; the CL/F was 39% lower than that of
carriers of the wild-type and heterozygous mutation. The tacrolimus CL/F
in patients who were co-administered glucocorticoids was 1.23-fold
higher than that in the control. According to the patient genotype and
combined use of glucocorticoids, 26 combinations of Wuzhi capsule and
tacrolimus doses were matched. The Monte Carlo simulation identified the
most suitable combination scheme. Conclusion: An improved tacrolimus PPK
model for patients with nephrotic syndrome was established and the most
suitable combination of Wuzhi capsule and tacrolimus doses was
identified, thus facilitating the selection of a more economical and
safe administration regimen.