Comparison of the pharmacokinetics of raltegravir given at 2 doses of 400 mg by swallowing versus one dose of 800 mg by chewing in healthy volunteers: A randomized, open-label, 2-period, single-dose, crossover phase 1 study

Dario Cattaneo, Maria V. Cossu, Serena Fucile, Agostino Riva, Sara Baldelli, Paola Meraviglia, Simona Landonio, Caterina Impagnatiello, Chiara Resnati, Massimo Galli, Emilio Clementi, Amedeo Capetti, Giuliano Rizzardini, Cristina Gervasoni

Research output: Contribution to journalArticle

Abstract

Background: The pharmacokinetics of raltegravir (RAL) in HIV patients is characterized by high interindividual and intraindividual variability. We documented previously that HIV patients taking RAL at 400 mg bid by chewing the tablets had significantly higher drug absorption and reduced pharmacokinetic variability than patients taking the drug by swallowing the tablets. This study extends our previous findings. Methods: An open-label, 2-period crossover study compared the pharmacokinetics of 2 doses of RAL given at 400 mg every 12 hours (that mimics a bid administration) by swallowing with 1 dose of 800 mg (that mimics a qd administration) by chewing the tablets in 12 healthy volunteers. RAL plasma concentrations were measured by a chromatographic method coupled with mass spectrometry. Results: Subjects taking RAL by chewing had significantly higher drug exposure (RAL area under the curve[AUC]0-24: 40722 ± 14843 versus 21753 ± 12229 ng·h/mL, P <0.0001) and reduced pharmacokinetic variability compared with those taking the drug by swallowing the whole tablet, with no difference in the minimum RAL concentrations (RAL Cmin: 36 ± 23 versus 43 ± 23 ng/mL, P = 0.298). Subjects taking RAL by chewing the tablets had significantly higher drug absorption and reduced pharmacokinetic variability compared with those taking the drug by swallowing. No differences were observed in the minimum RAL concentrations. Conclusions: RAL at 800 mg once daily by chewing the tablets may represent a novel therapeutic option for the treatment of HIV being associated with higher drug absorption, reduced pharmacokinetic variability, and potentially better compliance compared with patients swallowing the 400-mg bid intact tablets.

Original languageEnglish
Pages (from-to)119-125
Number of pages7
JournalTherapeutic Drug Monitoring
Volume37
Issue number1
DOIs
Publication statusPublished - Feb 2 2015

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Keywords

  • healthy volunteers
  • HIV
  • pharmacokinetics
  • Raltegravir

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

Cattaneo, D., Cossu, M. V., Fucile, S., Riva, A., Baldelli, S., Meraviglia, P., Landonio, S., Impagnatiello, C., Resnati, C., Galli, M., Clementi, E., Capetti, A., Rizzardini, G., & Gervasoni, C. (2015). Comparison of the pharmacokinetics of raltegravir given at 2 doses of 400 mg by swallowing versus one dose of 800 mg by chewing in healthy volunteers: A randomized, open-label, 2-period, single-dose, crossover phase 1 study. Therapeutic Drug Monitoring, 37(1), 119-125. https://doi.org/10.1097/FTD.0000000000000114