Document Detail

Influence of low-dose ritonavir with and without darunavir on the pharmacokinetics and pharmacodynamics of inhaled beclomethasone.
MedLine Citation:
PMID:  23535292     Owner:  NLM     Status:  MEDLINE    
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.
DESIGN: 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.
Sarita D Boyd; Colleen Hadigan; Maryellen McManus; Cheryl Chairez; Lynnette K Nieman; Alice K Pau; Raul M Alfaro; Joseph A Kovacs; Monica M Calderon; Scott R Penzak
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  63     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-13     Completed Date:  2013-08-29     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  355-61     Citation Subset:  IM; X    
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MeSH Terms
Anti-Inflammatory Agents / administration & dosage,  pharmacokinetics*,  therapeutic use
Beclomethasone / administration & dosage,  analogs & derivatives,  blood,  pharmacokinetics*,  therapeutic use
Drug Interactions
HIV Infections / drug therapy
HIV Protease Inhibitors / administration & dosage,  adverse effects,  therapeutic use
Middle Aged
Ritonavir / administration & dosage*,  adverse effects,  therapeutic use
Sulfonamides / administration & dosage*,  adverse effects,  therapeutic use
Young Adult
Grant Support
HHSN261200800001E//PHS HHS; Z99 AI999999/AI/NIAID NIH HHS
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/HIV Protease Inhibitors; 0/Sulfonamides; 5BGA9FD55H/beclomethasone 17-monopropionate; KGZ1SLC28Z/Beclomethasone; O3J8G9O825/Ritonavir; YO603Y8113/darunavir

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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