tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2015 Jun 22. pii: AAC.00069-15. [Epub ahead of print]
[h=1]A Drug-Disease Model Describing the Effect of Oseltamivir Neuraminidase Inhibition on Influenza Virus Progression.[/h] Kamal MA[SUP]1[/SUP], Gieschke R[SUP]2[/SUP], Lemenuel-Diot A[SUP]2[/SUP], Beauchemin CA[SUP]3[/SUP], Smith PF[SUP]4[/SUP], Rayner CR[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A population drug-disease model was developed to describe the time course of influenza virus with and without oseltamivir treatment, and to investigate opportunities for antiviral combination therapy. Data included viral titers from 208 subjects, across 4 studies, receiving placebo and oseltamivir 20 to 200 mg twice daily for 5 days. A 3-compartment mathematical model comprising target cells infected at rate β, free virus produced at rate p and cleared at rate c, and infected cells cleared at rate δ, was implemented in NONMEM with an inhibitory Hill function on virus production (p), accounting for the oseltamivir effect. In congruence with clinical data, the model predicts that the standard 75 mg regimen initiated 2 days after infection decreased viral shedding duration by 1.5 days versus placebo; the 150 mg regimen decreased shedding by an additional average 0.25 days. The model also predicts that initiating oseltamivir sooner post-infection, specifically at day 0.5 or 1, results in proportionally greater decreases in viral shedding duration, 5 and 3.5 days, respectively. Furthermore, the model suggests that combining oseltamivir (acting to subdue virus production rate) with an antiviral whose activity decreases viral infectivity (β) results in a moderate additive effect dependent on therapy initiation time. In contrast, the combination of oseltamivir with an antiviral whose activity increases viral clearance (c) shows significant additive effects independent of therapy initiation time. The utility of the model for investigating pharmacodynamic effects of novel antivirals alone or in combination on emergent influenza strains warrants further investigation.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26100715 [PubMed - as supplied by publisher]
[h=1]A Drug-Disease Model Describing the Effect of Oseltamivir Neuraminidase Inhibition on Influenza Virus Progression.[/h] Kamal MA[SUP]1[/SUP], Gieschke R[SUP]2[/SUP], Lemenuel-Diot A[SUP]2[/SUP], Beauchemin CA[SUP]3[/SUP], Smith PF[SUP]4[/SUP], Rayner CR[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A population drug-disease model was developed to describe the time course of influenza virus with and without oseltamivir treatment, and to investigate opportunities for antiviral combination therapy. Data included viral titers from 208 subjects, across 4 studies, receiving placebo and oseltamivir 20 to 200 mg twice daily for 5 days. A 3-compartment mathematical model comprising target cells infected at rate β, free virus produced at rate p and cleared at rate c, and infected cells cleared at rate δ, was implemented in NONMEM with an inhibitory Hill function on virus production (p), accounting for the oseltamivir effect. In congruence with clinical data, the model predicts that the standard 75 mg regimen initiated 2 days after infection decreased viral shedding duration by 1.5 days versus placebo; the 150 mg regimen decreased shedding by an additional average 0.25 days. The model also predicts that initiating oseltamivir sooner post-infection, specifically at day 0.5 or 1, results in proportionally greater decreases in viral shedding duration, 5 and 3.5 days, respectively. Furthermore, the model suggests that combining oseltamivir (acting to subdue virus production rate) with an antiviral whose activity decreases viral infectivity (β) results in a moderate additive effect dependent on therapy initiation time. In contrast, the combination of oseltamivir with an antiviral whose activity increases viral clearance (c) shows significant additive effects independent of therapy initiation time. The utility of the model for investigating pharmacodynamic effects of novel antivirals alone or in combination on emergent influenza strains warrants further investigation.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 26100715 [PubMed - as supplied by publisher]