Wada Kyoichi, Takada Mitsutaka, Sakai Mika, Ochi Hiroyuki, Kotake Takeshi, Okada Hiroshi, Morishita Hideki, Oda Noboru, Mano Akiko, Kato Tomoko S, Komamura Kazuo, Nakatani Takeshi
Department of Pharmacy, National Cardiovascular Center, Osaka, Japan.
J Heart Lung Transplant. 2009 Apr;28(4):409-11. doi: 10.1016/j.healun.2009.01.009.
This article reports changes in tacrolimus (FK506) blood levels connected with carbamazepine (CBZ). A drug interaction between FK506 and CBZ was investigated in a woman, who was in her 40s, who underwent heart transplantation. Pharmacokinetic parameters were measured, including dose and trough blood levels (C(0)), area under the serum concentration-time curve from 0 to 12 hours (AUC(0-12h)), and apparent clearance of oral FK506 (CL/F) for FK506 alone (about 3 months before starting CBZ) and combined with CBZ (11 days and about 3 months after starting CBZ). FK506 C(0) levels were decreased within 7 days of CBZ treatment. FK506 dosing required a 1.3- to 1.4-fold increase to maintain adequate blood levels while taking 200 mg CBZ daily. The AUC(0-12h)/dose 11 days after CBZ treatment was about 50% of the value before CBZ, and was about 70% at 3 months after CBZ treatment. The CL/F at 11 days and about 3 months after starting CBZ treatment was about 2 times higher than before CBZ therapy. FK506 C(0) levels are decreased by CBZ treatment, and blood levels should be closely monitored.
本文报道了他克莫司（FK506）血药浓度与卡马西平（CBZ）相关的变化。在一名40多岁接受心脏移植的女性中研究了FK506与CBZ之间的药物相互作用。测量了药代动力学参数，包括单独使用FK506（开始使用CBZ前约3个月）以及与CBZ联合使用时（开始使用CBZ后11天和约3个月）的剂量、谷血药浓度（C(0)）、0至12小时血清浓度-时间曲线下面积（AUC(0-12h)）以及口服FK506的表观清除率（CL/F）。CBZ治疗7天内FK506的C(0)水平降低。在每日服用200 mg CBZ时，为维持足够的血药浓度，FK506的给药剂量需要增加1.3至1.4倍。CBZ治疗11天后的AUC(0-12h)/剂量约为CBZ治疗前数值的50%，CBZ治疗3个月时约为70%。开始CBZ治疗11天和约3个月时的CL/F比CBZ治疗前高约2倍。CBZ治疗会降低FK506的C(0)水平，应密切监测血药浓度。
