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; N...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2008-01, Vol.31 (1), p.90-94
Main Authors: Takeuchi, Hironori, Matsuno, Naoto, Senuma, Kayoko, Hirano, Toshihiko, Yokoyama, Takayoshi, Taira, Shinichiro, Kihara, Yu, Kuzuoka, Kentaro, Konno, Osamu, Jojima, Yoshimaro, Mejit, Abudushukur, Akashi, Isao, Nakamura, Yuki, Iwamoto, Hitoshi, Hama, Koichiro, Iwahori, Tohru, Ashizawa, Tatsuto, Nagao, Takeshi, Toraishi, Tatsunori, Okuyama, Kiyoshi, Oka, Kitaro, Unezaki, Sakae
Format: Article
Language:English
Subjects:
Adult
Area Under Curve
Cyclosporine - blood
Cyclosporine - pharmacokinetics
Drug Monitoring
Female
Humans
Immunosuppressive Agents - blood
Immunosuppressive Agents - pharmacokinetics
Kidney Transplantation
Male
Tacrolimus - pharmacokinetics
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Summary: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).
ISSN:0918-6158