Quantitative management of the interaction of ritonavir on itraconazole plasma levels

Ref ID: 17775

Author:

L. Chouchana, I. Pierre, V. Poinsignon, E.M. Billaud*,
L. Weiss

Author address:

Paris, FR)

Full conference title:

22nd European Congress of Clinical Microbiology and Infectious Diseases

Abstract:

Objectives: Itraconazole (ITZ) is an antifungal agent extensively
metabolized by CYP3A4. It is largely involved in drug-drug
interactions (DDIs) as a potent enzymatic inhibitor. Therapeutic drug
monitoring (TDM) is required to optimize efficacy and safety,
especially because of its very long elimination half-life, of about
40 hours. We describe here the TDM-based management of the effect
of ritonavir on ITZ in a HIV patient.
Methods: ITZ, and its biologically active metabolite hydroxylitraconazole
(OH-ITZ), plasma concentrations are assayed by a
HPLC-Fluorometry method. ITZ dosage was adjusted to
maintain trough levels (C0) of (ITZ + OH-ITZ) sum in the range of
1-1.50 mg/L.
Results: A 40-year old HIV-infected patient admitted at the Infectious
Disease department exhibited skin injuries due to a disseminated
Penicillium marneffei infection. After 2 weeks of intravenous
amphotericin B, oral ITZ 400 mg/day is introduced (day 0). At
steady-state (day 10), ITZ and OH-ITZ through levels were,
respectively, 1.00 and 1.30 mg/L (sum 2.30 mg/L). Later on, in the
light of general clinical improvement and skin injuries resolution, a
highly active antiretroviral therapy (HAART), including darunavir/
ritonavir 600 mg/100 mg bid, is started on day 109. A plasma assay
realized 10 days after reveals that ITZ plasma level dramatically raised
to 4.80 mg/L, associated to an extensive metabolism blockade with
OH-ITZ at 0.70 mg/L. A dose reduction of daily ITZ intake by 2-fold
(200 mg/day), did not prevent extremely high plasma levels of ITZ and
OH-ITZ, respectively at 9.65 and 1.08 mg/L. Under TDM, ITZ was
stopped for 36 days and elimination half-life was assessed to be
increased at 17 days. ITZ has been reintroduced at a reduced dosage of
50 mg twice weekly, which has resulted in ITZ and OH-ITZ trough

Abstract Number: NULL

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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