Document Detail


Pharmacokinetic interaction between Amprenavir/Ritonavir and FosAmprenavir on cyclosporine in two patients with human immunodeficiency virus infection undergoing orthotopic liver transplantation.
MedLine Citation:
PMID:  16757288     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
G Guaraldi; S Cocchi; M Codeluppi; F Di Benedetto; S Bonora; A Motta; K Luzi; M Pecorari; W Gennari; M Masetti; G E Gerunda; R Esposito
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  Transplantation proceedings     Volume:  38     ISSN:  0041-1345     ISO Abbreviation:  Transplant. Proc.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-06-07     Completed Date:  2006-08-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0243532     Medline TA:  Transplant Proc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1138-40     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine and Medical Specialties, Infectious Diseases Clinic, University of Modena and Reggio Emilia, Italy. g.guaraldi@unimo.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-HIV Agents / pharmacokinetics*,  therapeutic use
Carbamates / pharmacokinetics*,  therapeutic use
HIV Infections / drug therapy*
Hepatitis C / surgery
Humans
Immunosuppressive Agents / pharmacokinetics*,  therapeutic use
Liver Transplantation / immunology*
Male
Metabolic Clearance Rate
Middle Aged
Phosphoric Acid Esters / pharmacokinetics*,  therapeutic use
Sulfonamides / pharmacokinetics*,  therapeutic use
Treatment Outcome
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Carbamates; 0/Immunosuppressive Agents; 0/Phosphoric Acid Esters; 0/Sulfonamides; 0/fosamprenavir; 161814-49-9/amprenavir

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