Pharmacokinetic interaction between Amprenavir/Ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation.
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.
Guaraldi
G
G
Department of Internal Medicine and Medical Specialties, Infectious Diseases Clinic, University of Modena and Reggio Emilia, Italy. g.guaraldi@unimo.it
Cocchi
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Codeluppi
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Di Benedetto
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Bonora
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Motta
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Luzi
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Pecorari
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Gennari
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Masetti
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Gerunda
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Esposito
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D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002219:Carbamates / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy*; D006526:Hepatitis C / Q000601:surgery; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010755:Organophosphates / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013449:Sulfonamides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D007166:Immunosuppressive Agents; D010755:Organophosphates; D013449:Sulfonamides; C095108:amprenavir; C426859:fosamprenavir