title: Evidence of different pharmacokinetics including relationship among AUC, peak, and trough levels between cyclosporine and tacrolimus in renal transplant recipients using new pharmacokinetic parameter--why cyclosporine is monitored by C(2) level and tacrolimus by trough level--.
abstract: The clinical efficacy of calcineurin inhibitors administered to renal transplant patients is considered to be a strong function of the area under the concentration time curve (AUC). Interestingly, monitoring timings of blood concentrations for two similar calcineurin inhibitors, cyclosporine (CYA; Neoral) and tacrolimus (TAC; Prograf) are different. Namely, CYA blood concentration is usually monitored at 2 h after administration (C(2)) substituted for peak concentration (C(p)) and TAC at trough concentration (C(t)). In the literature, data describing such characteristics of CYA and TAC have been presented in the past. However, each of these patient groups had different backgrounds. We have attempted to examine the behavior of blood concentration curves simultaneously for both CYA and TAC by establishing controlled groups of renal transplant patients with similar clinical backgrounds. Furthermore, we have analyzed the correlation with C(p) and C(t) versus AUC implementing area under the trough level (AUTL), or area above the trough level (AATL) as new pharmacokinetic parameters, such that C(2) for CYA and C(t) for TAC have been verified using controlled clinical data. We have also found distinct differences in the pharmacokinetics between CYA and TAC with the relationships between AUC, C(p), and C(t).
authors.affiliation: Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. take@ps.toyaku.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Naoto
authors.initials: N
authors.lastname: Matsuno
authors.forename: Kayoko
authors.initials: K
authors.lastname: Senuma
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Taira
authors.forename: Yu
authors.initials: Y
authors.lastname: Kihara
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kuzuoka
authors.forename: Osamu
authors.initials: O
authors.lastname: Konno
authors.forename: Yoshimaro
authors.initials: Y
authors.lastname: Jojima
authors.forename: Abudushukur
authors.initials: A
authors.lastname: Mejit
authors.forename: Isao
authors.initials: I
authors.lastname: Akashi
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Iwamoto
authors.forename: Koichiro
authors.initials: K
authors.lastname: Hama
authors.forename: Tohru
authors.initials: T
authors.lastname: Iwahori
authors.forename: Tatsuto
authors.initials: T
authors.lastname: Ashizawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagao
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Toraishi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Okuyama
authors.forename: Kitaro
authors.initials: K
authors.lastname: Oka
authors.forename: Sakae
authors.initials: S
authors.lastname: Unezaki
mesh_terms: D000328:Adult; D019540:Area Under Curve; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D016559:Tacrolimus / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus