Influence of method of systemic administration of adenovirus on virus-mediated toxicity: focus on mortality, virus distribution, and drug metabolism.

Introduction: Doses of 2 x 10(12) virus particles/kilogram (vp/kg) and higher of recombinant human adenovirus serotype 5 (HAdV-5) given via the tail vein induce significant toxicity and mortality in the rat. This was not observed when doses of 5.7 x 10(12) vp/kg were given through a surgically implanted jugular catheter.

Renal pathophysiology after systemic administration of recombinant adenovirus: changes in renal cytochromes P450 based on vector dose.

Recombinant adenovirus (Ad) significantly alters hepatic cytochrome P450 (CYP). Because changes in renal function can alter hepatic CYP, the effect of Ad on renal CYPs 4A1, 4A2, 4F1, and 2E1 was evaluated. Male Sprague-Dawley rats were given one of six intravenous doses (5.

Impact of transgene expression on drug metabolism following systemic adenoviral vector administration.

Background: Systemic administration of a first-generation adenovirus expressing E. coli beta-galactosidase (AdlacZ) alters expression and function of two hepatic drug-metabolizing enzymes, cytochrome P450 (CYP) 3A2 and 2C11, for 14 days. The objective of these studies was to determine how the transgene cassette influences CYP expression and function.