The purpose of the study was to elucidate human intestinal cytochrome P450 isoform(s) involved in the metabolism of an antihistamine, ebastine, having two major pathways of hydroxylation and N-dealkylation. The ebastine dealkylase in human intestinal microsomes was CYP3A4, based on the inhibition studies with antibodies against CYP1A, CYP2A, CYP2C, CYP2D, CYP2E, and CYP3A isoforms and their selective inhibitors. However, ebastine hydroxylase could not be identified. We then examined the inhibitory effects of anti-CYP4F antibody and 17-octadecynoic acid, an inhibitor of the CYP4 family, on ebastine hydroxylation in intestinal microsomes, since CYP4F was recently found to be the predominant ebastine hydroxylase in monkey intestine; and a novel CYP4F isoform (CYP4F12), also capable of hydroxylating ebastine, was found to exist in human intestine. However, the inhibitory effects were only partial (about 20%) and thus it was thought that, although human CYP4F was involved in ebastine hydroxylation, another predominant enzyme exists. Further screening showed that the hydroxylation was inhibited by arachidonic acid. CYP2J2 was selected as a candidate expressed in the intestine and closely related to arachidonic acid metabolism. The catalytic activity of recombinant CYP2J2 was much higher than that of CYP4F12. Anti-CYP2J antibody inhibited the hydroxylation to about 70% in human intestinal microsomes. These results demonstrate that CYP2J2 is the predominant ebastine hydroxylase in human intestinal microsomes. Thus, the present paper for the first time indicates that, in human intestinal microsomes, both CYP2J and CYP4F subfamilies not only metabolize endogenous substrates but also are involved in the drug metabolism. Ebastine is a potent nonsedative H 1 -receptor antagonist (Fig. 1), and after oral administration to experimental animals and humans, the agent is almost completely metabolized to the pharmacologically active principle, the carboxylated metabolite (carebastine), and other inactive metabolites Matsuda et al., 1994;Yamaguchi et al., 1994). Carebastine alone was the major metabolite detectable in the blood. Our previous in situ studies using rats indicated that the small intestine extensively converted the orally given ebastine to carebastine via hydroxylated ebastine and the dealkylated metabolite (Fujii et al., 1997). Therefore, it seemed that small intestine plays an important role in the first-pass metabolism of this drug, and the enzymes responsible for its metabolism exist there.We reported that ebastine was primarily metabolized by human liver microsomes to two metabolites, hydroxy-and desalkyl-ebastine (Hashizume et al., 1998). N-Dealkylation to desalkyl-ebastine was mediated by CYP3A4, whereas hydroxylation to hydroxy-ebastine, the most important intermediate metabolite yielding carebastine, was mediated by unidentified P450(s) other than CYP3A4. Our recent studies revealed that two novel CYP4F isoforms (P450 MI-2 and CYP4F12) obtained from monkey and human small intestine, respectively, were ...

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Following oral administration of [14C]loperamide hydrochloride in 1 mg/kg to rats, plasma levels of radioactivity reached maximum at 4 hrs and decreased with a half-life of 4.1 hrs. Radioactivity in 96-hr feces accounted for 95% of the dose, with 30% associated with unchanged drug, while that in urine only 3.5%. Radioactivity in 48-hr bile accounted for 42% of the dose associated entirely with metabolites. 3% of the dose was found at the level of the enterohepatic cycles. These findings show that about 70% of the dose with absorbed by intestine, the target tissue of the drug, a portion (30%) of which was excreted back into intestinal cavity after demethylation, while the remaining 40% transferred to liver by which it was extracted mostly, metabolized extensively and excreted largely into bile, as supported by in vitro demethylating activity in gut segments but none in gut contents, and by in situ marked hepatic extraction of the drug. Main metabolic pathways involved are described.

Uniformity of elements distribution in Cu2ZnSnS4 (CZTS) thin films were analyzed using X‐ray photoelectron spectroscopy (XPS) to improve of conversion efficiency on solar cells. The films were prepared from CuCl or CuCl2, ZnCl2, SnCl2, and thiourea by spray pyrolysis on quartz glass. The composition on surfaces of the as‐grown CZTS films was Cu‐poor and near stoichiometric compositions of Zn, Sn and S. In contrast to the surface, Cu‐rich and Sn‐poor compositions were obtained in the films. An existence of oxygen was observed on the film surface less than 20 nm. With increasing of thiourea concentration in the precursor, internal Cu composition, Cu/(Sn+Zn), was increased. S/metal ratio and Sn/Zn ratio in the films were less influenced by the thiourea concentration in the precursor solution. Cupper composition in the films was also affected a valence of Cu ion in the precursor. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

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A brand new thermal diffusivity measurement method was developed. In this new noncontact and absolute measurement method, thermal diffusivity was measured from infrared movie data. The model of one-dimensional thermal conduction was constructed by taking into account the thermal flow other than one-dimensional thermal conduction in the sample. On the basis of this thermal conduction model, the analytical equation for calculating thermal diffusivity was derived. A single-crystal sapphire plate was used as a test specimen for the new method. The test specimen was arranged to cause one-dimensional heat conduction. Infrared movies were taken by using an infrared camera at room temperature. Then, thermal diffusivity was numerically calculated from the acquired movie data using the analytical equation. It was experimentally demonstrated that thermal diffusivity was measured with an accuracy of around 10% error, from an infrared movie of a single-crystal sapphire sample.

Heavily B-doped SiGe thin films was reported to have large thermoelectric power and power factor at room temperature after annealing. In this paper, we investigated the structures that give rise to the large thermoelectric power and power factor. The thin films were prepared by ionbeam sputtering method. The annealing temperature dependence of structural properties was investigated. The thin films exhibited large thermoelectric power (1.4 mVK À1) and power factor (6:8 Â 10 À3 Wm À1 K À2) at room temperature after annealing at around 900 K. At that region, crystallite diameter was below 10 nm. The structure changed from amorphous to microcrystalline over 900 K. It is considered that quantum size effect enhances the thermoelectric power and power factor.

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