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Pharmacokinetics of nirmatrelvir/ritonavir and the drug-drug interaction with calcineurin inhibitor in renal transplant recipients
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Pharmacokinetics of nirmatrelvir/ritonavir and the drug-drug interaction with calcineurin inhibitor in renal transplant recipients
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Pharmacokinetics of nirmatrelvir/ritonavir and the drug-drug interaction with calcineurin inhibitor in renal transplant recipients
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Journal Article
Pharmacokinetics of nirmatrelvir/ritonavir and the drug-drug interaction with calcineurin inhibitor in renal transplant recipients
2024
Overview
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
C
0
/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.
Publisher
Springer Berlin Heidelberg,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Calcineurin Inhibitors - administration & dosage
/ Calcineurin Inhibitors - pharmacokinetics
/ Calcineurin Inhibitors - pharmacology
/ Cytochrome P-450 CYP3A - genetics
/ Cytochrome P-450 CYP3A - metabolism
/ Female
/ Genotype
/ High-performance liquid chromatography
/ Humans
/ Immunosuppressive Agents - administration & dosage
/ Immunosuppressive Agents - pharmacokinetics
/ Male
/ Ritonavir - pharmacokinetics
/ Tacrolimus - administration & dosage
/ Tacrolimus - pharmacokinetics
/ Toxicity
