A drug interaction study investigating the effect of Rifabutin on the pharmacokinetics of Maraviroc in healthy subjects

M Ghannad, M Dennehy, C la Porte, I Seguin, D Tardiff, R Mallick, E Sabri, G Zhang, S Kanji, D W Cameron, M Ghannad, M Dennehy, C la Porte, I Seguin, D Tardiff, R Mallick, E Sabri, G Zhang, S Kanji, D W Cameron

Abstract

Effects of steady-state rifabutin on the pharmacokinetics of steady-state maraviroc were investigated in fourteen healthy adult female and male volunteers. Maraviroc 300 mg twice daily (BID) was given orally with food for fifteen days. On day six, rifabutin 300 mg once daily (QD, P.O.) was added to the regimen. Formal pharmacokinetic (PK) sampling was performed on days five and fifteen. Individual plasma drug concentration-time data for maraviroc, and rifabutin on day fifteen, were obtained using validated High Performance Liquid Chromatography (HPLC) tandem Mass Spectrometry (MS/MS). Rifabutin steady state exposure was comparable to data in the literature. Maraviroc area under the curve (AUC) and minimum plasma concentration (Clast or Cmin) were reduced by 17% and 30% respectively when co-administered with rifabutin. No unexpected or serious adverse eventsoccurred. Based on the reduced exposure of maraviroc observed in this study, increasing the dose of maraviroc may be studied to normalize its moderately reduced exposure following rifabutin co-administration, a moderate inducer of CYP3A4.

Trial registration: ClinicalTrials.gov NCT01894776.

Conflict of interest statement

ViiV Healthcare, a Pfizer affiliate, funded this study. CLP began working for Janssen after the conclusion of the study. Janssen had no role in this study and did not contribute any funding. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. CONSORT flow diagram [12].
Fig 1. CONSORT flow diagram [12].
Fig 2. Study timeline.
Fig 2. Study timeline.
Fig 3
Fig 3
Steady-state geometric mean Maraviroc concentration-time profile (log-scale) for subjects receiving Maraviroc alone (squares and solid line) and Maraviroc plus Rifabutin (circles and dashed line)(A). Steady-state maraviroc concentration-time profile (log-scale) for individual participants without (B) and with rifabutin (C) co-administration.
Fig 4
Fig 4
Steady-state geometric mean (log-scale) Rifabutin (A) and 25-O-desacetyl Rifabutin (B) concentration-time profile for participants receiving Maraviroc and Rifabutin.
Fig 5. Effect of steady-state Rifabutin on…
Fig 5. Effect of steady-state Rifabutin on the steady-state Maraviroc AUC, Cmax, Clast for individual subjects.

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