Variability of Zaleplon 5-Oxidase Activity in Mice and Humans, and Inhibition by Raloxifene.

Background: Zaleplon (ZAL) is a sedative-hypnotic agent, which is mainly metabolized to inactive 5-oxidized zaleplon (5-oxo-ZAL) and N-des-ethylated ZAL (des-ethyl-ZAL) in mice and humans. The former reaction is considered to be catalyzed by aldehyde oxidase present in liver cytosol.

Methods: Here, we examined sex and strain differences of ZAL metabolism to 5-oxo-ZAL among four strains of mice, as well as the inter-individual variation in humans, in order to evaluate the variability of 5-oxo-ZAL-forming activity and its relationship with aldehyde oxidase activity.

Study of the usefulness of patch testing and use test to predict the safety of commercial topical drugs.

Patch testing (PT) can be used to identify allergens and irritants responsible for contact allergic and irritant dermatitis, respectively. However, the reproducibility of PT and correlation between PT and use test has not been fully evaluated. The aim of the present study was to examine the reproducibility of PT and its usefulness in assessing the safety of topical drugs.

Prediction of human metabolism of the sedative-hypnotic zaleplon using chimeric mice transplanted with human hepatocytes.

1. Human chimeric mice (h-PXB mice) having humanized liver, constructed by transplantation of human hepatocytes, were evaluated as an experimental model for predicting human drug metabolism. Metabolism of zaleplon in h-PXB mice was compared with that in rat chimeric mice (r-PXB mice) constructed by transplantation of rat hepatocytes.

Strain difference of oxidative metabolism of the sedative-hypnotic zaleplon by aldehyde oxidase and cytochrome P450 in vivo and in vitro in rats.

The in vivo and in vitro metabolism of the sedative-hypnotic agent zaleplon (ZAL) to 5-hydroxylated ZAL (5-oxo-ZAL) and N-desethylated ZAL (desethyl-ZAL) was studied in four strains of rats. Incubation of ZAL with liver microsomes afforded desethyl-ZAL via cytochrome P450-catalyzed reaction, with little strain difference. In contrast, incubation of ZAL with liver cytosol afforded 5-oxo-ZAL with marked strain differences.

Analysis of Trichophyton antigen-induced contact hypersensitivity in mouse.

Background: Trichophyton-induced superficial skin mycosis is a common infectious human disease, but the immunological mechanism against Trichophyton infection is unclear with regard to many points. Since Trichophyton cannot colonize mice, guinea pigs were used in previous experiments on Trichophyton infection. However, it is difficult to perform immunological and genetic analyses in guinea pigs.