Clinical implication of therapeutic drug monitoring on voriconazole from the aspect of the analysis for CYP2C19 gene

• Published in: Japanese journal of antibiotics Vol. 63; no. 3; p. 255
• Main Authors: Kimura, Masao, Yamagishi, Yuka, Kawasumi, Noriyo, Hagihara, Mao, Hasegawa, Takaaki, Mikamo, Hiroshige
• Format: Journal Article
• Language: Japanese
• Published: Japan 01.06.2010
• Subjects: Adult; Aged; Aged, 80 and over; Antifungal Agents - blood; Aryl Hydrocarbon Hydroxylases - genetics; Cytochrome P-450 CYP2C19; Drug Monitoring; Female; Humans; Liver - drug effects; Male; Middle Aged; Pyrimidines - adverse effects; Pyrimidines - blood; Pyrimidines - pharmacokinetics; Triazoles - adverse effects; Triazoles - blood; Triazoles - pharmacokinetics; Voriconazole
• ISSN: 0368-2781

Three microsome enzymes are involved in voriconazole (VRCZ) metabolism, CYP2C19, CYP3A4 and CYP2C9, and subjects classified as poor metabolizers (PM), which would include about 20% of Japanese population, had higher serum VRCZ concentrations than other subjects. Also, because VRCZ appears hepatotoxicity and visual disturbance in side effect, VRCZ must be done therapeutic drug monitoring (TDM). This study evaluated the three cases which administered VRCZ to analysis for CYP2C19 gene. This study evaluated VRCZ trough concentration and side effect in the fifteen cases which administered VRCZ to analysis for TDM in Aichi University Hospital. Also, the administering design of VRCZ followed drug information in the three cases. Correlation of VRCZ trough concentration and dosage was weak in fifteen cases. In case 1, although patient is not PM, trough concentration of VRCZ showed high concentration (8.43 microg/mL) after 4 days of starting administration and appeared side effects of illusion and optical illusion. In case 2, although patient is PM, trough concentration of VRCZ showed 5.53 microg/mL and 8.61 microg/mL after 4 days and 7 days of starting administration, respectively, also liver function (AST, ALT and others) rised slightly. In case 3, although patient is not PM, trough concentration of VRCZ after the 5 days and 12 days of starting administration showed 3.2 microg/mL and 3.25 microg/mL, respectively, also maintained therapeutic trough lebel. In this result, it was thought that pharmacokinetics of VRCZ was unstable comparatively and concentration of VRCZ varied generally among individuals regardless of the CYP2C19 genotype. Therefore, it was important to an individual patient to improve a clinical effect, and to decrease the adverse event from the initial administering design, and is necessary to do the administering design afterwards while doing TDM at many times.