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Nirmatrelvir increases blood tacrolimus concentration in COVID-19 patients as determined by UHPLC-MS/MS method.
Wu, Q-G; Zeng, L-Y; Li, F; Zhu, Z-Q; Yin, L; Meng, X-M; Zhang, L; Zhang, P; Jiang, X-H; Ling, Y; Zhang, L-J.
  • Wu QG; Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. zhanglijun5028@dingtalk.com.
Eur Rev Med Pharmacol Sci ; 27(2): 818-825, 2023 01.
Article in English | MEDLINE | ID: covidwho-2237093
ABSTRACT

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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Tacrolimus / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Eur Rev Med Pharmacol Sci Journal subject: Pharmacology / Toxicology Year: 2023 Document Type: Article Affiliation country: Eurrev_202301_31083

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Tacrolimus / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Eur Rev Med Pharmacol Sci Journal subject: Pharmacology / Toxicology Year: 2023 Document Type: Article Affiliation country: Eurrev_202301_31083