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--.
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).
Takeuchi
Hironori
H
Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. take@ps.toyaku.ac.jp
Matsuno
Naoto
N
Senuma
Kayoko
K
Hirano
Toshihiko
T
Yokoyama
Takayoshi
T
Taira
Shinichiro
S
Kihara
Yu
Y
Kuzuoka
Kentaro
K
Konno
Osamu
O
Jojima
Yoshimaro
Y
Mejit
Abudushukur
A
Akashi
Isao
I
Nakamura
Yuki
Y
Iwamoto
Hitoshi
H
Hama
Koichiro
K
Iwahori
Tohru
T
Ashizawa
Tatsuto
T
Nagao
Takeshi
T
Toraishi
Tatsunori
T
Okuyama
Kiyoshi
K
Oka
Kitaro
K
Unezaki
Sakae
S
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*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus