title: Influence of low-dose ritonavir with and without darunavir on the pharmacokinetics and pharmacodynamics of inhaled beclomethasone.
abstract: OBJECTIVE
  To identify an alternative inhaled corticosteroid to fluticasone propionate that can be safely coadministered with HIV protease inhibitors, the safety and pharmacokinetics of beclomethasone dipropionate (BDP) and its active metabolite, beclomethasone 17-monopropionate (17-BMP), in combination with ritonavir (RTV) and darunavir/ritonavir (DRV/r) were assessed.
  
  
  METHODS
  Open-label, prospective, randomized pharmacokinetic and pharmacodynamic study in healthy volunteers.
  
  
  METHODS
  Thirty healthy volunteers received inhaled 160 μg bid BDP for 14 days and were then randomized (1:1:1) into 3 groups: group 1 (control) remained on BDP alone for 28 days, group 2 received 100 mg bid BDP + RTV for 28 days, and group 3 received 600/100 mg bid BDP + DRV/r for 28 days. Pharmacokinetic sampling for 17-BMP was performed on days 14 and 28, and pharmacokinetic parameter values were compared within patients and between groups. Cortisol stimulation testing was also performed on days 1, 14, 28, and 42 and compared within and between groups.
  
  
  RESULTS
  Geometric mean ratios (day 28:day 14) (90% confidence interval) for 17-BMP area under the concentration-time curve in groups 1, 2, and 3, respectively, were 0.93 (0.81 to 1.06, P = 0.27), 2.08 (1.52 to 2.65, P = 0.006), and 0.89 (0.68 to 1.09, P = 0.61). There were no significant reductions in serum cortisol levels within or between groups (P > 0.05).
  
  
  CONCLUSIONS
  DRV/r did not increase 17-BMP exposure, whereas RTV alone produced a statistically significant but clinically inconsequential 2-fold increase in 17-BMP exposure. Adrenal suppression was not observed in any of the study groups. These data suggest that BDP can be safely coadministered with DRV/r and likely other RTV-boosted protease inhibitors.
authors.affiliation: Office of Safety and Epidemiology, US Food and Drug Administration, Silver Spring, MD 20993, USA. sarita.boyd@fda.hhs.gov
authors.forename: Sarita D
authors.initials: SD
authors.lastname: Boyd
authors.forename: Colleen
authors.initials: C
authors.lastname: Hadigan
authors.forename: Maryellen
authors.initials: M
authors.lastname: McManus
authors.forename: Cheryl
authors.initials: C
authors.lastname: Chairez
authors.forename: Lynnette K
authors.initials: LK
authors.lastname: Nieman
authors.forename: Alice K
authors.initials: AK
authors.lastname: Pau
authors.forename: Raul M
authors.initials: RM
authors.lastname: Alfaro
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kovacs
authors.forename: Monica M
authors.initials: MM
authors.lastname: Calderon
authors.forename: Scott R
authors.initials: SR
authors.lastname: Penzak
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001507:Beclomethasone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069454:Darunavir; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C065857:beclomethasone 17-monopropionate; D001507:Beclomethasone; D019438:Ritonavir; D000069454:Darunavir
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