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.
Pharmacokinetic interaction between Amprenavir/Ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation
BONORA, Stefano;
2006-01-01
Abstract
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.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
