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In vitro-in vivo model for evaluating the antiviral activity of amprenavir in combination with ritonavir administered at 600 and 100 milligrams, respectively, every 12 hours

Preston, Sandra L ; Piliero, Peter J ; Bilello, John A ; Stein, Daniel S ; Symonds, William T ; Drusano, George L

Antimicrobial agents and chemotherapy, November 2003, Vol.47(11), pp.3393-9 [Peer Reviewed Journal]

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  • Title:
    In vitro-in vivo model for evaluating the antiviral activity of amprenavir in combination with ritonavir administered at 600 and 100 milligrams, respectively, every 12 hours
  • Author: Preston, Sandra L ; Piliero, Peter J ; Bilello, John A ; Stein, Daniel S ; Symonds, William T ; Drusano, George L
  • Description: The study objective was to evaluate the pharmacodynamics of amprenavir in an in vitro system, develop an exposure target for maximal viral suppression, and determine the likelihood of target attainment based on the pharmacokinetics of amprenavir and ritonavir in human immunodeficiency virus (HIV)-infected patients. Population pharmacokinetic data were obtained from 13 HIV-infected patients receiving amprenavir and ritonavir in doses of 600 and 100 mg, respectively, every 12 h. A 2,500-subject Monte Carlo simulation was performed. Target attainment was also estimated for a target derived from clinical data. Maximal viral suppression (in vitro) was achieved when amprenavir free-drug concentrations remained greater than four times the 50% effective concentration (EC(50)) for 80% of the dosing interval. At an amprenavir EC(50) of 0.03 microM, the likelihood of target attainment is 97.4%. For reduced-susceptibility isolates for which the EC(50)s are 0.05 and 0.08 microM, target attainment is...
  • Is Part Of: Antimicrobial agents and chemotherapy, November 2003, Vol.47(11), pp.3393-9
  • Identifier: ISSN: 0066-4804 ; PMID: 14576093 Version:1
  • Subjects: Anti-HIV Agents -- Pharmacology ; Antiviral Agents -- Pharmacology ; Ritonavir -- Pharmacology ; Sulfonamides -- Pharmacology
  • Language: English

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