title: Effect of intestinal P-glycoprotein on daily tacrolimus trough level in a living-donor small bowel recipient.
abstract: We have examined whether the expression levels of the intestinal absorptive barriers, MDR1 gene product P-glycoprotein and cytochrome P450 IIIA4 (CYP3A4), correlate with the trough levels of orally administered tacrolimus in a recipient of small bowel transplant for 4 months. By using a competitive polymerase chain reaction, the expression of MDR1 messenger RNA (mRNA) and CYP3A4 mRNA by intestinal cells in a part of the mucosa biopsy specimen was evaluated. The average mRNA expression levels of MDR1 and CYP3A4 were 8.6 and 39.6 amol/microg total RNA, respectively. Both the MDR1 and CYP3A4 mRNA levels changed markedly throughout this period. The tacrolimus concentration/dose ratio correlated well with the mRNA expression level of MDR1, but not CYP3A4. These results suggested that intestinal P-glycoprotein rather than CYP3A4 is a good probe to predict the intraindividual variation in the tacrolimus pharmacokinetics during immunosuppressant therapy after small bowel transplantation.
authors.affiliation: Department of Pharmacy, Kyoto University Hospital, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Masuda
authors.forename: S
authors.initials: S
authors.lastname: Uemoto
authors.forename: T
authors.initials: T
authors.lastname: Hashida
authors.forename: Y
authors.initials: Y
authors.lastname: Inomata
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Inui
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism*; D002675:Child, Preschool; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism* / Q000637:transplantation*; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012313:RNA; D012333:RNA, Messenger / Q000737:chemistry; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*; D014184:Transplantation, Homologous
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; C034477:RNA primers; D012333:RNA, Messenger; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D016559:Tacrolimus