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Pharmacokinetics of nirmatrelvir/ritonavir and the drug-drug interaction with calcineurin inhibitor in renal transplant recipients.
- Source :
-
European Journal of Clinical Pharmacology . Aug2024, Vol. 80 Issue 8, p1219-1227. 9p. - Publication Year :
- 2024
-
Abstract
- Objectives: To describe the pharmacokinetic (PK) characteristics of nirmatrelvir/ritonavir in renal transplant recipients and explore the potential factors that related to the PK variance of nirmatrelvir/ritonavir and its interaction with calcineurin inhibitor (CNI). Methods: Renal transplant recipients treated with CNI and nirmatrelvir/ritonavir were prospectively enrolled. Steady-state plasma concentrations of nirmatrelvir/ritonavir were determined by high-performance liquid chromatography-tandem mass spectrometry, and the PK parameters were calculated using non-compartmental analysis. Spearman correlation analysis was used for exploring influencing factors. Results: A total of eight recipients were enrolled; for nirmatrelvir and ritonavir, AUC/dose was 0.24179 ± 0.14495 and 0.06196 ± 0.03767 μg·h·mL-1·mg-1. Red blood cell (RBC), hematocrit (Ht), hemoglobins (Hb), and creatinine clearance (Ccr) were negatively correlated with AUC/dose of nirmatrelvir, while Ccr, CYP3A5 genotype, and CYP3A4 genotype were related to the AUC/dose of ritonavir. Ccr was negatively correlated with the C0/dose of tacrolimus (TAC) after termination of nirmatrelvir/ritonavir (rs = -0.943, p = 0.008). Conclusions: The PK characteristics of nirmatrelvir/ritonavir vary greatly among renal transplant recipients. Factors including Ccr and CYP3A5 genotype were related to the in vivo exposure of nirmatrelvir/ritonavir. During the whole process before and after nirmatrelvir/ritonavir therapy, it is recommended to adjust the CNI basing on renal function to avoid CNI toxicity exposure. [ABSTRACT FROM AUTHOR]
- Subjects :
- *KIDNEY physiology
*KIDNEY transplantation
*HIGH performance liquid chromatography
*PATIENTS
*TRANSPLANTATION of organs, tissues, etc.
*LIQUID chromatography-mass spectrometry
*ERYTHROCYTES
*DATA analysis
*RECEIVER operating characteristic curves
*CREATININE
*RESEARCH funding
*ENZYME inhibitors
*HEMOGLOBINS
*TERMINATION of treatment
*IN vivo studies
*PROTEASE inhibitors
*LONGITUDINAL method
*DRUG interactions
*STATISTICS
*HEMATOCRIT
*TACROLIMUS
*RITONAVIR
*GENOTYPES
Subjects
Details
- Language :
- English
- ISSN :
- 00316970
- Volume :
- 80
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- European Journal of Clinical Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 178295790
- Full Text :
- https://doi.org/10.1007/s00228-024-03691-9