Telazol, a 1:1 combination of
tiletamine HCl and
zolazepam HCl, is an
anesthetic and immobilizing agent that has been in use in veterinary medicine and animal field studies for more than a decade. No information is available, however, regarding the effects of
Telazol, or its constituents, on hepatic
cytochromes P450. The purpose of the present study was to assess the effect of
Telazol on the rat hepatic
cytochrome P450 system. Adult male rats were given a single
intraperitoneal injection of
Telazol dose at a of 20, 40, 80, or 120 mg/kg
body weight (six rats/dose), while control rats received the vehicle only. Animals were killed 24 hr later, and hepatic microsomes were prepared. Treatment with
Telazol resulted in dose-dependent increases in
benzyloxyresorufin O-dealkylase and
testosterone 16 beta-hydroxylase activities.
Ethoxyresorufin O-deethylase,
p-nitrophenol hydroxylase, and
testosterone 6 beta- and
7 alpha-hydroxylase activities were essentially unaltered at all doses of the
drug. Densitometric quantitation of immunoblots probed with polyclonal antibody against
cytochrome P450 2B1 indicated a 17-fold increase in the hepatic level of
cytochrome P450 2B1 for rats treated with the highest dose of
Telazol. In contrast, the level of
cytochrome P450 2B2 was increased slightly but not significantly. In the presence of 0.5 mg of anti-
cytochrome P450 2B1 IgG/nmol P450,
benzyloxyresorufin O-dealkylase activity was inhibited by 92% in hepatic microsomes prepared from a rat treated with
Telazol at a dose of 120 mg/kg compared with only 25% inhibition in hepatic microsomes from a control rat. In summary, the results demonstrate that
Telazol specifically induced expression of the
cytochrome P450 2B
isozymes in rats.