Pharmacokinetic interaction between amprenavir/ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation
Pharmacokinetic interaction between amprenavir/ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation
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DOI：
10.1016/j.transproceed.2006.02.013
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发表时间：
2006-05-01
影响因子：
0.9
通讯作者：
Esposito, R
中科院分区：
文献类型：
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作者：
Guaraldi, G;Cocchi, S;Esposito, R
高效抗逆转录病毒治疗（HAART）和免疫抑制药物之间的药代动力学相互作用是管理接受原位肝移植（OLT）的人类免疫缺陷病毒感染患者的关键因素。我们描述了共同管理的安普那韦/利托那韦（APV/R）和磷安普那韦（FosAPV）的环孢素（CsA）浓度在两名患者接受OLT终末期肝病由于丙型肝炎病毒的影响。患者1维持300 mg CsA，每日2次，谷浓度（C-trough）约为250 ng/mL，移植后12天重新开始HAART，每日2次，300 mg APV/r，相应的APV C-trough为5293 ng/mL，RTV C-tough为186 ng/mL。HAART开始后48 h，CsA的C-trogh为1200 mg/mL，因此需要将CsA剂量减少12倍（每天50 mg）才能达到治疗效果。在患者2中，维持300 mg CsA，每日两次，相应的C谷值为400 ng/mL，在OLT后12天重新开始HAART，FosAPV 1400 mg，每日两次。48小时后，CsA的C谷值约为600 ng/mL，FosAPV的C谷值为1221 ng/mL。在这种情况下，有必要将CsA给药减少3.5倍（每天175 mg）。总之，治疗药物监测是必要的，以监测HAART和CsA后OLT，以防止由于这两种疗法的毒性。使用FosAPV而不使用利托那韦加强足以维持足够的CsA血药浓度，避免任何毒性事件。
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-tough of 186 ng/mL. Forty-eight hours after initiation of HAART, C-trogh 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.