title: Increased bioavailability of tacrolimus after rectal administration in rats.
abstract: The oral bioavailability of tacrolimus is low and varies considerably in humans due to first-pass metabolism by cytochrome P450 (CYP) 3A4 and the active efflux mediated by P-glycoprotein. This study was undertaken to elucidate the usefulness of rectal administration of tacrolimus as an alternative route to improve its bioavailability. Tacrolimus powder was suspended in a suppository base (witepsol H-15) and the tacrolimus suppository was inserted into the anus of the rats. For comparison, tacrolimus was suspended in 0.5% sodium methylcellulose solution and administered orally to rats. The dose of tacrolimus was fixed to 2 mg/kg. Blood samples were collected periodically up to 24 h after dosing, and tacrolimus concentrations were assayed by microparticle enzyme immunoassay. The whole blood concentrations of tacrolimus after rectal administration were much greater than those after oral administration. The C(max) and AUC(0-24 h) values after rectal administration were 3.9- and 6.9-fold greater than those after oral administration, respectively. These results clearly suggest a possibility that rectal administration of tacrolimus is capable of improving its bioavailability and cutting the costs of tacrolimus treatment.
authors.affiliation: Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, 207 Aza Uehara, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakai
authors.forename: Norio
authors.initials: N
authors.lastname: Hobara
authors.forename: Nobuo
authors.initials: N
authors.lastname: Hokama
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kameya
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohshiro
authors.forename: Matao
authors.initials: M
authors.lastname: Sakanashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saitoh
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013488:Suppositories; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D013488:Suppositories; D016559:Tacrolimus