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

Détails

ID Serval
serval:BIB_B50E136DB0CD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Ritonavir-boosted atazanavir-lopinavir combination: a pharmacokinetic interaction study of total, unbound plasma and cellular exposures
Périodique
Antiviral Therapy
Auteur(s)
Colombo  S., Buclin  T., Franc  C., Guignard  N., Khonkarly  M., Tarr  P. E., Rochat  B., Biollaz  J., Telenti  A., Decosterd  L. A., Cavassini  M.
ISSN
1359-6535 (Print)
Statut éditorial
Publié
Date de publication
2006
Volume
11
Numéro
1
Pages
53-62
Notes
Clinical Trial
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Résumé
OBJECTIVES: 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). DESIGN: 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. METHODS: 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. RESULTS: 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/Ctot ratio was unaffected by the addition of the second PI and remained stable throughout dosing interval. Good correlations were observed between Ccell, Cu and Ctot for each drug. No relevant toxicity was observed. CONCLUSIONS: Adding LPV to ATV did not influence the plasma and cellular PK parameters of ATV. Adding ATV to LPV caused a limited decrease in LPV concentrations. The clinical significance of this decrease is unknown and warrants further investigation to determine the need for tailoring LPV dosage in selected cases.
Mots-clé
Adult Blood Proteins/metabolism Drug Interactions Drug Therapy, Combination Female HIV Infections/*drug therapy/virology HIV Protease Inhibitors/administration & dosage/adverse effects/metabolism/*pharmacokinetics Humans Male Middle Aged Oligopeptides/administration & dosage/adverse effects/metabolism/*pharmacokinetics Protein Binding Pyridines/administration & dosage/adverse effects/metabolism/*pharmacokinetics Pyrimidinones/administration & dosage/adverse effects/metabolism/*pharmacokinetics Ritonavir/administration & dosage/adverse effects/metabolism/*pharmacokinetics Treatment Outcome
Pubmed
Web of science
Création de la notice
24/01/2008 20:44
Dernière modification de la notice
20/08/2019 15:23
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