A pharmacokinetic-pharmacodynamic model to optimize the phase IIa development program of maraviroc

Journal of Acquired Immune Deficiency Syndromes : JAIDS
Maria C RosarioElna van der Ryst

Abstract

To use a viral dynamics model to compare the effectiveness of in vivo viral inhibition of several doses of maraviroc (MVC;UK-427,857) and to use a modeling approach to support design decisions for a monotherapy study using various dosing regimens of maraviroc given with and without food. The pharmacokinetic-pharmacodynamic model was developed using clinical data from a first monotherapy study (study A4001007). This was a randomized, double-blind, placebo-controlled, multicenter study of maraviroc in 44 asymptomatic HIV-1-infected patients. Patients received maraviroc under food restrictions at 25 mg once daily or 50, 100, or 300 mg twice daily, or placebo for 10 days. Antiviral responses were assessed by measuring plasma HIV-1 RNA levels during screening, during randomization, at baseline, and daily during the 10 days of treatment and at days 11 to 15, 19, 22, 25, and 40. An integrated pharmacokinetic-pharmacodynamic model was developed using the mixed effects modeling approach with patients' pharmacokinetic profiles on the last day of treatment, HIV-1 RNA levels over time, and the individual viral susceptibility. The parameters derived from the viral dynamic model were used to calculate average viral inhibition fraction, decay...Continue Reading

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Citations

Mar 6, 2010·Journal of Pharmacokinetics and Pharmacodynamics·Philippe JacqminJanet R Wade
May 23, 2012·Journal of Pharmacokinetics and Pharmacodynamics·Holger DetteWeng Kee Wong
Jun 28, 2012·Journal of Pharmacokinetics and Pharmacodynamics·Jing Fang, Pravin R Jadhav
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Jul 30, 2015·The Journal of Antimicrobial Chemotherapy·Marco SiccardiAndrew Owen
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Oct 12, 2007·Drugs·Natalie J Carter, Gillian M Keating
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Nov 29, 2012·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Anthony MillsSimon Portsmouth

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