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KMID : 1146920220520010109
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Journal of Pharmaceutical Investigation
2022 Volume.52 No. 1 p.109 ~ p.127
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Population pharmacokinetic analysis of lornoxicam in healthy Korean males considering creatinine clearance and CYP2C9 genetic polymorphism
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Jeong Seung-Hyun
Jang Ji-Hun
Lee Yong-Bok
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Abstract
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Purpose: Lornoxicam is a drug that is used for various diseases related to inflammation and pain. In the clinical application of lornoxicam, studies on individualized pharmacotherapy and modeling considering interindividual pharmacokinetic variability have rarely been reported. In this study, a population pharmacokinetic modeling study was performed with a search for effective covariates that could explain the interindividual pharmacokinetic variability of lornoxicam.
Methods: Based on the bioequivalence results of 28 healthy Korean males and the identification of various genetic and physicochemical parameters of the participants, a population pharmacokinetic modeling of lornoxicam was performed by a non-linear mixed-effects modeling method using Phoenix NLME.
Results: The pharmacokinetics of lornoxicam in the population were well explained by the one-compartment basic model with first-order absorption/elimination and lag-time reflected in the absorption phase. The covariates investigated to account for interindividual pharmacokinetic variability were extended to the established basic model. Creatinine clearance (CrCl), which is used as a general indicator of renal function, was positively correlated with the clearance of lornoxicam, and this was identified as a valid covariate in the population pharmacokinetic model of lornoxicam. According to the genetic polymorphism of CYP2C9, a significant difference was confirmed in the clearance of lornoxicam, which was also a valid covariate in the model.
Conclusion: Considering that the metabolism of lornoxicam is mainly by the CYP2C9 enzyme and a significant proportion of the metabolite is excreted in the urine through the kidneys, it was appropriate to explore the CYP2C9 genotype and CrCl levels as covariates in the population pharmacokinetic model of lornoxicam. Through the results of this study, individualized and effective lornoxicam therapy taking into account the genotype and degree of renal function of individuals will be possible in the future.
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KEYWORD
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Lornoxicam, Population pharmacokinetic modeling, Healthy Korean males, CYP2C9, Creatinine clearance
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