title: Pharmacokinetic interaction between indinavir and darunavir with low-dose ritonavir in healthy volunteers.
abstract: OBJECTIVE
  To investigate the potential for a pharmacokinetic interaction between darunavir (DRV, TMC114, Prezista), indinavir (IDV, Crixivan) and low-dose ritonavir (RTV, Norvir).
  
  
  METHODS
  In three 7-day sessions, 17 HIV-negative healthy volunteers received treatment A (DRV/r 400/100 mg b.i.d.), treatment B (IDV/r 800/100 mg b.i.d.) and treatment C (DRV/r 400/100 mg b.i.d. + IDV 800 mg b.i.d.). On day 7, full pharmacokinetic profiles of DRV, IDV and RTV were determined. Safety and tolerability were also assessed.
  
  
  RESULTS
  Based on the least-squares means ratios, the steady-state exposure (area under the curve, AUC(12h)) and plasma concentrations (C(min) and C(max)) of IDV were increased by 23, 125 and 8%, respectively, when DRV was co-administered. The co-administration of IDV with DRV/r resulted in increases of 24, 44 and 11% for, respectively, DRV AUC(12h), C(min) and C(max), compared with administration of DRV/r alone. Eight volunteers discontinued due to an adverse event. Overall, adverse events and laboratory abnormalities were more commonly reported during treatments including IDV.
  
  
  CONCLUSIONS
  When used in combination with DRV/r, dose adjustment of IDV from 800 mg b.i.d. to 600 mg b.i.d. may be warranted in cases of intolerance.
authors.affiliation: Tibotec Inc., Yardley, Pa., USA. vsekar @ tibus.jnj.com
authors.forename: Vanitha
authors.initials: V
authors.lastname: Sekar
authors.forename: Eric
authors.initials: E
authors.lastname: Lefebvre
authors.forename: Tine
authors.initials: T
authors.lastname: De Marez
authors.forename: Martine
authors.initials: M
authors.lastname: De Pauw
authors.forename: Els
authors.initials: E
authors.lastname: De Paepe
authors.forename: Tony
authors.initials: T
authors.lastname: Vangeneugden
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000069454:Darunavir; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D010949:Plasma / Q000737:chemistry; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D013449:Sulfonamides; D019469:Indinavir; D019438:Ritonavir; D000069454:Darunavir