Effect of a modified saquinavir/ritonavir dosing regimen with lower dose lead-in phase on QTc interval, pharmacokinetics, antiviral activity and safety in treatment-naïve HIV-1-infected patients

Drugs in R&D
Marta BoffitoPeter N Morcos

Abstract

Saquinavir/ritonavir (1000/100 mg twice daily [BID]) is associated with dose- and exposure-dependent prolongation of the QT interval. The QT risk is considered higher during the first week of therapy, when saquinavir peak exposure has been observed. A modified regimen with a lower dose lead-in phase may reduce potential saquinavir-/ritonavir-induced QT prolongations. To explore the effect of the modified saquinavir/ritonavir regimen on QT interval, pharmacokinetics, antiviral activity, and safety in treatment-naïve HIV-1-infected patients. Twenty-three HIV-1-infected treatment-naïve patients received saquinavir/ritonavir 500/100 mg BID on days 1-7 and 1000/100 mg BID on days 8-14 in combination with two nucleoside reverse transcriptase inhibitors. The primary endpoint was mean maximum change from dense predose baseline in QT values corrected using Fridericia's formula (∆QTcFdense) across study days. Secondary endpoints included maximum change from time-matched baseline in QTcF, antiviral activity, pharmacokinetics, and safety over the 14 days. The mean maximum ∆QTcFdense was 3, 1, 7, 12, and 7 ms on days 3, 4, 7, 10, and 14, respectively. Across all study days, 2/21 patients had a maximum ∆QTcFdense ≥30 ms (on day 10); the high...Continue Reading

References

Oct 16, 2004·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Marta BoffitoAnton Pozniak
Nov 30, 2006·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Margaret A Chesney
Sep 28, 2007·Clinical Pharmacology and Therapeutics·K SinghM Boffito
Dec 17, 2008·British Journal of Clinical Pharmacology·Beny CharbitChristian Funck-Brentano
Feb 14, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Sharon WalmsleyFrançois Raffi
Dec 1, 2011·The Annals of Pharmacotherapy·Kimberley HuntCara Hills-Nieminen

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Citations

May 11, 2017·Beilstein Journal of Organic Chemistry·S ArshadiE Ghorbani-Kalhor
Oct 7, 2017·Current Opinion in HIV and AIDS·Roger C McIntoshBarry E Hurwitz
Sep 26, 2020·Access Microbiology·S J ShepherdR N Gunson

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Clinical Trials Mentioned

NCT01638650

Software Mentioned

WinNonlin
Cardiocore

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