title: Mechanisms of lower maintenance dose of tacrolimus in obese patients.
abstract: A retrospective analysis suggested that blood tacrolimus concentrations were consistent among patients with a body mass index (BMI) that was lean (<18.5), normal (≥ 18.5 and <25) or overweight/obese (≥ 25). The average maintenance dose of tacrolimus in patients with BMI ≥ 25 was significantly lower compared with that in patients with a BMI of less than 25. Lean and obese Zucker rats fed a normal diet were given tacrolimus intravenously or orally. The blood concentrations of tacrolimus in obese rats were significantly higher than those in lean rats after administration via both routes. The moment analysis has suggested that CLtot and Vdss of tacrolimus were not significantly different between lean and obese rats. The bioavailability was higher in obese rats, compared with that in lean rats. The protein expression of Cyp3a2 in the liver was significantly decreased in obese rats, compared with lean rats, while P-gp in the small intestine was also significantly decreased in obese rats. These results suggested that the steady-state trough concentration of tacrolimus in obese patients was well maintained by a relatively low dose compared with that in normal and lean patients, presumably due to increased bioavailability.
authors.affiliation: Department of Hospital Pharmacy, University Hospital, Kanazawa University.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sawamoto
authors.forename: Tran T
authors.initials: TT
authors.lastname: Huong
authors.forename: Natsumi
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mizutani
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Sai
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Miyamoto
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D015992:Body Mass Index; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D051381:Rats; D011924:Rats, Zucker; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus