Drug-drug Interactions and Initial Dosage Optimization of Tacrolimus in Patients with Myasthenia Gravis Based on Population Pharmacokinetic Analysis: Impact of Vitamin D2 Soft Capsules
Wei Shen, Guan-Ying Zhang, Jie Wang, Xi-Ran Wang, Jia-Yi Du, Shi-Yuan Zhao, Zhi-Hao Ping, Su-Mei He, Hai-Bo Zhang, Dong-Dong WangIntroduction:
Tacrolimus is considered an important immunosuppressant for myasthenia gravis (MG); however, patients with MG often use multiple medications concurrently, increasing their risk of interactions with tacrolimus. The present study investigated drug-drug interactions (DDIs) and optimized the initial tacrolimus dosing in patients with MG using population pharmacokinetic (PPK) analysis.
Methods:
Data from patients with MG receiving tacrolimus therapy were retrospectively collected between February 2023 and October 2025 from the Affiliated Hospital of Xuzhou Medical University. Inclusion criteria: (a) Patients with MG, (b) Treatment with tacrolimus, (c) Therapeutic drug monitoring (TDM) for tacrolimus. Exclusion criteria: MG patients with missing clinical medical record data, pregnancy/lactation. Nonlinear mixed-effect modeling (NONMEM) was used to build a PPK model, and the Monte Carlo method was used for simulate tacrolimus concentrations in patients with MG.
Results:
The final model suggested that weight and vitamin D2 soft capsule significantly affected the clearance rate of tacrolimus in patients with MG. When patients with MG were not taking vitamin D2 soft capsules simultaneously, the initial tacrolimus dosing was as follows: for patients weighing 50-78 kg, 0.06 mg/kg was recommended; for patients weighing 78-100 kg, 0.04 mg/kg was recommended. When patients with MG take vitamin D2 soft capsules simultaneously, the initial tacrolimus dosage was as follows: for patients weighing 50-60 kg, 0.10 mg/kg was recommended; for patients weighing 60-100 kg, 0.08 mg/kg was recommended.
Discussion:
Among patients with the same weight, when combined with vitamin D2 soft capsule, the clearance rate of tacrolimus in patients with MG increased by 31%, which was a very interesting finding.
Conclusion:
This study investigated DDIs and optimized the initial dosing of tacrolimus in patients with MG based on PPK analysis and found that when patients with MG take vitamin D2 soft capsule simultaneously, the initial dosages of tacrolimus may need to be increased accordingly.