Guaraldi G, Cocchi S, Codeluppi M, Di Benedetto F, Bonora S, Motta A, Luzi K, Pecorari M, Gennari W, Masetti M, Gerunda G E, Esposito R
Department of Internal Medicine and Medical Specialties, Infectious Diseases Clinic, University of Modena and Reggio Emilia, Italy.
Transplant Proc. 2006 May;38(4):1138-40. doi: 10.1016/j.transproceed.2006.02.013.
The pharmacokinetic interaction between highly active antiretroviral therapy (HAART) and immunosuppressive drugs is a critical element in the management of patients with human immunodeficiency virus infection who undergo orthotopic liver transplantation (OLT). We describe the effect of the coadministration of Amprenavir/Ritonavir (APV/r) and FosAmprenavir (FosAPV) on cyclosporine (CsA) concentrations in two patients receiving OLT for end-stage liver disease due to hepatitis C Virus. Patient 1, who was maintained on 300 mg CsA twice a day with a trough concentration (C(trough)) around 250 ng/mL, restarted HAART 12 days after transplantation with 300 mg APV/r twice a day with corresponding APV C(trough) of 5293 ng/mL and RTV C(trough) of 186 ng/mL. Forty-eight hours after initiation of HAART, C(trough) of CsA was 1200 mg/mL, so it was necessary to reduce the CsA dosage 12-fold (50 mg every day) to achieve a therapeutic effect. In Patient 2, who was maintained on 300 mg CsA twice a day and a corresponding C(trough) of 400 ng/mL, HAART was restarted 12 days post-OLT with FosAPV 1400 mg twice a day. After 48 hours C(trough) of CsA was around 600 ng/mL and C(trough) of FosAPV, 1221 ng/mL. In this case it was necessary to reduce the CsA administration 3.5-fold (175 mg every day). In conclusion, therapeutic drug monitoring was necessary to monitor HAART and CsA post-OLT to prevent toxicity due to both therapies. The use of FosAPV without ritonavir boostering is sufficient to maintain adequate CsA blood concentrations, avoiding any event of toxicity.
高效抗逆转录病毒疗法（HAART）与免疫抑制药物之间的药代动力学相互作用，是接受原位肝移植（OLT）的人类免疫缺陷病毒感染患者治疗管理中的关键因素。我们描述了安普那韦/利托那韦（APV/r）和福沙那韦（FosAPV）联合给药对两名因丙型肝炎病毒导致终末期肝病而接受OLT的患者环孢素（CsA）浓度的影响。患者1每天服用300 mg CsA，谷浓度（C(trough)）约为250 ng/mL，移植后12天重新开始HAART，每天两次服用300 mg APV/r，相应的APV C(trough)为5293 ng/mL，RTV C(trough)为186 ng/mL。开始HAART 48小时后，CsA的C(trough)为1200 mg/mL，因此有必要将CsA剂量减少12倍（每天50 mg）以达到治疗效果。患者2每天服用300 mg CsA，相应的C(trough)为400 ng/mL，OLT术后12天重新开始HAART，每天两次服用1400 mg福沙那韦。48小时后，CsA的C(trough)约为600 ng/mL，福沙那韦的C(trough)为1221 ng/mL。在这种情况下，有必要将CsA给药量减少3.5倍（每天175 mg）。总之，OLT术后有必要进行治疗药物监测，以监测HAART和CsA，防止两种疗法导致的毒性。在不使用利托那韦增强的情况下使用福沙那韦足以维持足够的CsA血药浓度，避免任何毒性事件。
