Biol. Pharm. Bull., 31(1),90-94, January 2008

Regular Articles

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-

Hironori TAKEUCHI,^*,a Naoto MATSUNO,^b Kayoko SENUMA,^a Toshihiko HIRANO,^d Takayoshi YOKOYAMA,^b Shinichiro TAIRA,^b Yu KIHARA,^b Kentaro KUZUOKA,^b Osamu KONNO,^b Yoshimaro JOJIMA,^b Abudushukur MEJIT,^b Isao AKASHI,^b Yuki NAKAMURA,^b Hitoshi IWAMOTO,^b Koichiro HAMA,^b Tohru IWAHORI,^b Tatsuto ASHIZAWA,^b Takeshi NAGAO,^b Tatsunori TORAISHI,^c Kiyoshi OKUYAMA,^c Kitaro OKA,^d and Sakae UNEZAKI^a

^a Department of Practical Pharmacy, Tokyo University of Pharmacy and Life Sciences; ^d Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences; 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan: ^b Department of Fifth Surgery, Hachioji Medical Center, Tokyo Medical University; and ^c Department of Pharmaceutics, Hachioji Medical Center, Tokyo Medical University; 1163 Tatemachi, Hachioji, Tokyo 193-0998, Japan. * To whom correspondence should be addressed. e-mail: take@ps.toyaku.ac.jp

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 (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 C₂ 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.

Key words area under the trough level; cyclosporine; tacrolimus; trough concentration; blood concentration at 2 h after administration; area under the concentration time curve