Eur Rev Med Pharmacol Sci 2023; 27 (2): 818-825
DOI: 10.26355/eurrev_202301_31083

Nirmatrelvir increases blood tacrolimus concentration in COVID-19 patients as determined by UHPLC-MS/MS method

Q.-G. Wu, L.-Y. Zeng, F. Li, Z.-Q. Zhu, L. Yin, X.-M. Meng, L. Zhang, P. Zhang, X.-H. Jiang, Y. Ling, L.-J. Zhang

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. zhanglijun5028@dingtalk.com


OBJECTIVE: Transplant recipients have a higher risk of SARS-CoV-2 infection owing to the use of immunosuppressive drugs like tacrolimus (FK506). FK506 and nirmatrelvir (NMV) (an anti-SARS-CoV-2 drug) are metabolized by cytochrome P450 3A4 and may have potential drug-drug interactions. It is important to determine the effect of NMV on FK506 concentrations.

PATIENTS AND METHODS: Following protein precipitation from blood, FK506 and its internal standard (FK506-13C,2d4) were detected by ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). Total 22 blood samples (valley concentrations) from two coronavirus disease 2019 (COVID-19) patients were collected and analyzed for FK506 concentrations.

RESULTS: Blood levels of FK506 (0.5-100 ng/mL) showed good linearity. The UHPLC-MS/MS method was validated with intra- and inter-batch accuracies of 104.55-107.85%, and 99.52-108.01%, respectively, and precisions of < 15%. Mean blood FK506 concentration was 12.01 ng/mL (range, 3.15-33.1 ng/mL). Five-day co-administration with NMV increased the FK506 concentrations from 3.15 ng/mL to 33.1 ng/mL, returning to 3.36 ng/mL after a 9-day-washout.

CONCLUSIONS: We developed a simple quantification method for therapeutic drug monitoring of FK506 in patients with COVID-19 using UHPLC-MS/MS with protein precipitation. We found that NMV increased FK506 blood concentration 10-fold. Therefore, it is necessary to re-consider co-administration of FK506 with NMV.

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To cite this article

Q.-G. Wu, L.-Y. Zeng, F. Li, Z.-Q. Zhu, L. Yin, X.-M. Meng, L. Zhang, P. Zhang, X.-H. Jiang, Y. Ling, L.-J. Zhang
Nirmatrelvir increases blood tacrolimus concentration in COVID-19 patients as determined by UHPLC-MS/MS method

Eur Rev Med Pharmacol Sci
Year: 2023
Vol. 27 - N. 2
Pages: 818-825
DOI: 10.26355/eurrev_202301_31083