Pharmacokinetic Behavior of Cyclosporine A in Liver Dysfunction

Kihira Kenji

Kadoyama Masayuki

Miyake Katsushi

Kitaura Teruaki

Kimura Yasuhiro

Yoshida Minoru

Fukuchi Hiroshi

Hiroshima Journal of Medical Sciences

[PISSN] 0018-2052

[EISSN] 2433-7668

[NCID] AA00664312

The pharmacokinetic behavior of cyclosporine A (CyA), known as a potential immunosuppressive agent to prevent graft rejection in transplantation, was studied in patients with acute hepatitis and primary biliary cirrhosis (PBC). The ratios of blood concentration of total CyA (CyA and its metabolites), CyA, and CyA metabolites to dose/kg body weight, (t-CyA/dose, CyA/dose, and CyA-Met/dose, respectively) were significantly higher in patients with hepatitis than those in renal transplantation. In PBC patients these ratios showed a tendency to be smaller than those in renal transplantation, but were not significant. The ratio of CyA-Met/ CyA was higher in the patients with hepatitis and PBC than that in renal transplantation. It was highest in the patients with PBC. The ratio of CyA-Met/CyA was significantly increased with a decrease of liver functions evaluated by serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and total serum bilirubin (t-Bil). These results indicate that hepatic function affects the pharmacokinetic behavior of CyA and the increased ratio of CyA-Met/dose could be caused by a possible increased efflux of metabolites into the blood circulation due to impaired bile excretion. These results also indicate the importance of therapeutic drug monitoring (TDM) in the use of CyA with patients with hepatic dysfunction.

Cyclosporine A

Renal transplantation

Acute hepatitis

Primary biliary cirrhosis

Medical sciences [ 490 ]

eng

Hiroshima University Medical Press

[ISSN] 0018-2052

[NCID] AA00664312