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