- 作者: Zdenek Zidek; Pavel Anzenbacher; Eva Anzenbacherova; Evzen Buchar; Eva Kmonickova; Petr Potmesil; Antonin Holy
- 作者服務機構: 1 Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague 4, Czech Republic; ; 2 Faculty of Medicine, Institute of Pharmacolgy, Palacky University, Hn憝ot璯sk?3, 775 15, Olomouc, Czech Republic;; 3 Faculty of Medicine, Institute of Medical Chemistry and Biochemistry, Palacky University, Hn憝ot璯sk?3, 775 15, Olomouc, Czech Republic; ; 4 Faculty of Medicine in Pilsen, Institute of Pharmacology, Charles University, Karlovarska 48, 301 66, Pilsen, Czech Republic; ; 5 Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 166 10, Prague 6, Czech Republic
- 中文摘要: --
- 英文摘要: Interference of antiviral agent adefovir, i.e. 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) with microsomal drug metabolizing system was investigated in rats. The content of total liver cytochrome P450 (CYP) was lowered while that of its denaturated form, P420, was elevated in animals intraperitoneally treated with PMEA (25 mg/kg). Similar effect was observed after treatment with a prodrug of adevofir, adefovir dipivoxil (bisPOM-PMEA). The CYP2E1-dependent formation of 4-nitrocatechol from 77-nitrophenol was diminished, though the specific activity of 4-nitrophenol hydroxylase remained unchanged. PMEA had no influence on expression of CYP2E1 protein and mRNA and mRNAs of other P450 isoenzymes (1A1, 1A2, 2C11, 3A1, 3A2, and 4A1). It may be concluded that repeated systemic administration of higher doses of PMEA results in a partial degradation of rat CYP protein to inactive P420.
- 中文關鍵字: --
- 英文關鍵字: adefovir, CYP2E1, cytochrome 450, PMEA