title: 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.
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 C(min): 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.
authors.affiliation: *Unit of Clinical Pharmacology; †Department of Infectious Diseases; ‡Clinical Pharmacology Unit, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Università degli Studi di Milano, Milan; §Scientific Institute E. Medea, Bosisio Parini, Italy; and ¶School of Clinical Medicine, Faculty of Health Science, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Dario
authors.initials: D
authors.lastname: Cattaneo
authors.forename: Maria V
authors.initials: MV
authors.lastname: Cossu
authors.forename: Serena
authors.initials: S
authors.lastname: Fucile
authors.forename: Agostino
authors.initials: A
authors.lastname: Riva
authors.forename: Sara
authors.initials: S
authors.lastname: Baldelli
authors.forename: Paola
authors.initials: P
authors.lastname: Meraviglia
authors.forename: Simona
authors.initials: S
authors.lastname: Landonio
authors.forename: Caterina
authors.initials: C
authors.lastname: Impagnatiello
authors.forename: Chiara
authors.initials: C
authors.lastname: Resnati
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
authors.forename: Amedeo
authors.initials: A
authors.lastname: Capetti
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.forename: Cristina
authors.initials: C
authors.lastname: Gervasoni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D018592:Cross-Over Studies; D003679:Deglutition; D005260:Female; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008409:Mastication; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D013607:Tablets; D055815:Young Adult
chemical_list: D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D013607:Tablets; D000068898:Raltegravir Potassium