1. Drug-virus interaction: effect of administration of recombinant adenoviruses on the pharmacokinetics of docetaxel in a rat model.
- Author
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Wonganan P, Zamboni WC, Strychor S, Dekker JD, and Croyle MA
- Subjects
- Adenoviridae genetics, Adenoviridae metabolism, Animals, Antineoplastic Agents, Phytogenic pharmacokinetics, Cytochrome P-450 CYP3A, Disease Models, Animal, Docetaxel, Gene Expression Regulation, Enzymologic drug effects, Liver drug effects, Liver virology, Male, Rats, Rats, Sprague-Dawley, Transaminases blood, Aryl Hydrocarbon Hydroxylases metabolism, Cytochrome P-450 Enzyme Inhibitors, Genetic Vectors genetics, Liver metabolism, Membrane Proteins metabolism, Taxoids pharmacokinetics
- Abstract
Modern cancer therapy combines recombinant viruses with traditional chemotherapeutic agents that are metabolized by hepatic cytochrome P450 3A4 (CYP3A4). A single dose of recombinant adenovirus (Ad) expressing beta-galactosidase (AdlacZ) significantly alters CYP3A2, the correlate of CYP3A4, in rats for 14 days. Recombinant adenovirus expressing human p53 (Adp53) also suppresses CYP3A2. Plasma clearance of docetaxel (DTX) in animals given AdlacZ (3.38+/-0.22 l h(-1) kg(-1)) was significantly lower than that of those given DTX alone (7.35+/-1.22 l h(-1) kg(-1), P
- Published
- 2009
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