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 C2 Level and Tacrolimus by Trough Level

• Published in: Biological & Pharmaceutical Bulletin 2008/01/01, Vol.31(1), pp.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: area under the concentration time curve; area under the trough level; blood concentration at 2 h after administration; cyclosporine; tacrolimus; trough concentration
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.90

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 (C2) substituted for peak concentration (Cp) and TAC at trough concentration (Ct). 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 Cp and Ct versus AUC implementing area under the trough level (AUTL), or area above the trough level (AATL) as new pharmacokinetic parameters, such that C2 for CYA and Ct 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, Cp, and Ct.