title: Pharmacokinetic interaction between darunavir boosted with ritonavir and omeprazole or ranitidine in human immunodeficiency virus-negative healthy volunteers.
abstract: Darunavir (DRV; TMC114; Prezista) is a human immunodeficiency virus (HIV) protease inhibitor used in combination with low-dose ritonavir (RTV) (DRV/r) as a pharmacokinetic enhancer. Protease inhibitor absorption may be decreased during coadministration of drugs that limit stomach acid secretion and increase gastric pH. This study was conducted to investigate the effect of ranitidine and omeprazole on the plasma pharmacokinetics of DRV and RTV in HIV-negative healthy volunteers. Sixteen volunteers completed the study and received DRV/r, DRV/r plus ranitidine, and DRV/r plus omeprazole, in three separate sessions. Treatment was given for 4 days with an additional morning dose on day 5, and regimens were separated by a washout period of 7 days. Samples were taken over a 12-h period on day 5 for the assessment of DRV and RTV plasma concentrations. Pharmacokinetic parameters assessed included DRV area under the curve, maximum plasma concentration, and trough plasma concentration. The least-squares mean ratios and 90% confidence intervals are reported with treatment of DRV/r alone as a reference. Compared with DRV/r alone, no significant changes in DRV pharmacokinetic parameters were observed during coadministration of DRV/r and either ranitidine or omeprazole. Treatment regimens were generally well tolerated, and no serious adverse events were reported. In conclusion, coadministration of DRV/r and ranitidine or omeprazole was well tolerated by the volunteers. Ranitidine and omeprazole did not have a significant influence on DRV pharmacokinetics. No dose adjustments are required when DRV/r is coadministered with omeprazole or ranitidine.
authors.affiliation: Tibotec Inc., 1020 Stony Hill Road, Suite 300, Yardley, PA 19067, USA. VSekar@tibus.jnj.com
authors.forename: Vanitha J
authors.initials: VJ
authors.lastname: Sekar
authors.forename: Eric
authors.initials: E
authors.lastname: Lefebvre
authors.forename: Els
authors.initials: E
authors.lastname: De Paepe
authors.forename: Tine
authors.initials: T
authors.lastname: De Marez
authors.forename: Martine
authors.initials: M
authors.lastname: De Pauw
authors.forename: Wim
authors.initials: W
authors.lastname: Parys
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000897:Anti-Ulcer Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D000069454:Darunavir; D004347:Drug Interactions; D005260:Female; D006635:Histamine H2 Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D011899:Ranitidine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D000897:Anti-Ulcer Agents; D000998:Antiviral Agents; D006635:Histamine H2 Antagonists; D013449:Sulfonamides; D011899:Ranitidine; D009853:Omeprazole; D019438:Ritonavir; D000069454:Darunavir