PMID: 16518960Mar 8, 2006Paper

Ritonavir-boosted atazanavir-lopinavir combination: a pharmacokinetic interaction study of total, unbound plasma and cellular exposures

Antiviral Therapy
Sara ColomboMatthias Cavassini

Abstract

To assess potential pharmacokinetic (PK) interactions between atazanavir (ATV, 300 mg, once daily) and lopinavir (LPV, 400 mg, twice daily), both boosted by ritonavir (RTV, 100 mg). Two-parallel groups, addition of LPV in patients receiving ATV (n=6), and addition of ATV in patients receiving LPV (n=7), with before/after comparisons. Each group had two complete PK profiles before and 2 weeks after the addition of the second protease inhibitor (PI). Total plasma concentrations (Ctot) were analysed by HPLC-UV and unbound plasma concentrations (Cu) and cellular concentrations (Ccell) were analysed by LC-MS/MS. Plasma and cellular PK parameters were also calculated. Unbound and cellular fractions were expressed as Cu/Ctot and Ccell/Ctot ratio. Data were analysed by paired Student t-test on log values; correlations between Ccell, Cu and Ctot were explored by log-log linear regression. Adding LPV to ATV did not influence the plasma and cellular PK parameters of ATV. Adding ATV to LPV was associated with a decrease in LPV concentrations (by 16% for area under the time-concentration curve, maximum concentration and trough concentration, NS; and by 35% for Cmin, P=0.04). The RTV PK parameters remained unmodified. The Ccell/Ctot and Cu/C...Continue Reading

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