open access

https://hdl.handle.net/2115/89360

Hepatic drug metabolism in older people with body composition changes

英語

skeletal muscle mass

2022-05-01

John Wiley & Sons

Geriatrics & gerontology international

22(5)

449-454

Aim Dosage adjustment is essential in older individuals because they are prone to experience a decline in liver function and changes in body composition. However, quantitative tests or equations for evaluating the activity of hepatic drug metabolism have not yet been clearly established. We examined hepatic drug metabolism activities in older individuals, focusing on changes in body composition parameters. Methods Lansoprazole and nifedipine, substrates of the metabolic enzymes cytochrome P450 (CYP) 2C19 and 3A4, respectively, were selected to study hepatic drug metabolism. Residual samples from blood test for older patients were evaluated to determine drug metabolism. The body composition of relevant patients was determined by analyzing characteristic parameters of skeletal muscle mass index (SMI), handgrip strength (HGS) and hepatic steatosis index (HSI). The differences in hepatic drug metabolism were studied statistically among categories in terms of the cut-off value of these parameters. Results Older male patients receiving lansoprazole and nifedipine in the low SMI (<7.0 kg/m(2)) category showed an 85-90% reduction in respective CYP2C19 and CYP3A4 metabolic activities compared with the normal SMI category. For the female patients, CYP2C19 and CYP3A4 metabolic activities showed no significant correlation with SMI and HGS. Fatty liver disease (HSI >= 36) was found to reduce CYP2C19 metabolic activity particularly in older female patients. Conclusions Low CYP2C19 metabolic activity was statistically correlated with low SMI in male patients and high HSI in female patients, whereas low CYP3A4 metabolic activity was statistically correlated with low HGS in male patients.

学術雑誌論文

Accepted Manuscript

This is the peer reviewed version of the following article: Kaburaki, S, Yoshimura, E, Miyamoto, Y, et al. Hepatic drug metabolism in older people with body composition changes. Geriatr. Gerontol. Int. 2022; 22: 449– 454. which has been published in final form at 10.1111/ggi.14380. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.

1444-1586