title: Species differences in intestinal glucuronidation activities between humans, rats, dogs and monkeys.
abstract: 1.  Glucuronidation via UDP-glucuronosyltransferase (UGT) in the intestine has been reported to influence the pharmacokinetics (PK) of drugs; however, information concerning the differences in activity between species is limited. Here, we investigated the in vitro and in vivo activities of intestinal glucuronidation for 17 UGT substrates in humans, rats, dogs and monkeys. 2.  Although in vitro intrinsic clearance (CLint,u,UGT) in intestinal microsomes showed a good correlation between humans and laboratory animals, values tended to be lower in humans than in laboratory animals. The ratio of CLint,u,UGT in the absence and presence of bovine serum albumin differed between species. In vivo, the fraction of drug absorbed (FaFg) in humans correlated with that in dogs and monkeys, but not in rats. 3.  While an inverse correlation between CLint,u,UGT and FaFg was observed in each species, the CLint,u,UGT values in the intestinal microsomes corresponding to FaFg values in dogs were three to four times higher than in other animals. 4.  These results indicate the need for a degree of caution when extrapolating PK data from laboratory animals to humans.
authors: Analysis and Pharmakokinetics Research Laboratories, Astellas Pharma Inc , Ibaraki , Japan.
authors: Takako
authors: T
authors: Furukawa
authors: Yoichi
authors: Y
authors: Naritomi
authors: Kazuhiro
authors: K
authors: Tetsuka
authors: Fumihiro
authors: F
authors: Nakamori
authors: Hiroyuki
authors: H
authors: Moriguchi
authors: Katsuhiro
authors: K
authors: Yamano
authors: Shigeyuki
authors: S
authors: Terashita
authors: Kenji
authors: K
authors: Tabata
authors: Toshio
authors: T
authors: Teramura
mesh_terms: D000818:Animals; D019817:Benzoic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D004285:Dogs; D005965:Glucuronates / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008252:Macaca fascicularis; D008657:Metabolic Clearance Rate / Q000502:physiology*; D008861:Microsomes / Q000378:metabolism; D008954:Models, Biological; D051381:Rats; D012710:Serum Albumin, Bovine; D013045:Species Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D005965:Glucuronates; D012710:Serum Albumin, Bovine; D019817:Benzoic Acid; D014453:Glucuronosyltransferase