Physiologically Based Pharmacokinetic (PBPK) Modeling of Lornoxicam: Exploration of doses for CYP2C9 Genotypes and Patients with Cirrhosis.
| Autor: | Jeong SH; College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA., Jang JH; College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, 14214, USA., Lee YB; College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea. Electronic address: leeyb@chonnam.ac.kr. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of pharmaceutical sciences [J Pharm Sci] 2022 Nov; Vol. 111 (11), pp. 3174-3184. Date of Electronic Publication: 2022 Sep 01. |
| DOI: | 10.1016/j.xphs.2022.08.035 |
| Abstrakt: | Lornoxicam physiologically based pharmacokinetic (PBPK) models were developed and validated on the basis of clinical pharmacokinetic results obtained by considering CYP2C9 genetic polymorphisms in healthy adult populations. PBPK models were extended to predict lornoxicam pharmacokinetics for patients with cirrhosis by quantitatively examining the pathophysiological information associated with cirrhosis. The predicted plasma exposure to lornoxicam was approximately 1.12-2.83 times higher in the CYP2C9*1/*3 and *1/*13 groups than in the CYP2C9*1/*1 group of healthy adult populations and patients with cirrhosis. The predicted plasma exposure to lornoxicam was approximately 1.28-3.61 times higher in patients with cirrhosis than in healthy adult populations. If the relationship between lornoxicam exposure in plasma and drug efficacy was proportional, then the proposed adjusted doses of lornoxicam for each group varied from 1.25 mg to 8 mg. As the severity of cirrhosis increased, or when the CYP2C9 genotype was *1 heterozygous, the dose adjustment range of lornoxicam increased. Therefore, the effect of pathophysiological factors (cirrhosis severity) on the pharmacokinetics of lornoxicam might be more important than that of CYP2C9 genetic factors. These results could be useful for broadening the scope of clinical application of lornoxicam by enabling dose selection based on CYP2C9 genotypes and liver cirrhosis degree. Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this study to disclose. (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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