PMID- 27162626
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160510
LR  - 20200930
IS  - 2045-8932 (Print)
IS  - 2045-8940 (Electronic)
IS  - 2045-8932 (Linking)
VI  - 6
IP  - Suppl 1
DP  - 2016 Mar
TI  - Effects of omeprazole and aluminum hydroxide/magnesium hydroxide on riociguat 
      absorption.
PG  - S43-8
LID - 10.1086/682228 [doi]
AB  - Riociguat, a soluble guanylate cyclase stimulator, is a novel therapy for the 
      treatment of pulmonary hypertension. Riociguat bioavailability is reduced in 
      neutral versus acidic conditions and therefore may be affected by concomitant use 
      of medications that increase gastric pH. The effect of coadministration of the 
      proton pump inhibitor omeprazole or the antacid AlOH/MgOH on the 
      pharmacokinetics, safety, and tolerability of riociguat 2.5 mg was characterized 
      in two open-label, randomized, crossover studies in healthy males. In study 1, 
      subjects pretreated for 4 days with omeprazole 40 mg received cotreatment with 
      omeprazole plus riociguat or riociguat alone (no pretreatment) on day 5 (n = 12). 
      In study 2, subjects received cotreatment with 10 mL AlOH/MgOH plus riociguat or 
      riociguat alone (n = 12). Pre- and cotreatment with omeprazole decreased 
      riociguat bioavailability (mean decreases in area under the plasma 
      concentration-time curve [AUC] and maximum concentration in plasma [C max] were 
      26% and 35%, respectively). Cotreatment with AlOH/MgOH resulted in greater 
      decreases in riociguat bioavailability (mean decreases in AUC and C max were 34% 
      and 56%, respectively). In both studies, most adverse events (AEs) were of mild 
      intensity, and no serious AEs were reported. No additional safety signals were 
      identified. Treatment with riociguat, with or without omeprazole or AlOH/MgOH, 
      was well tolerated, with a good safety profile. Owing to the resulting increase 
      of gastric pH, riociguat bioavailability is reduced by coadministration with 
      AlOH/MgOH and, to a lesser extent, by coadministration with omeprazole. Thus, 
      antacids should not be administered within an hour of receiving riociguat, but no 
      dose adjustment is required for coadministration of proton pump inhibitors.
FAU - Becker, Corina
AU  - Becker C
AD  - Clinical Pharmacology, Pharma Research Center, Bayer Pharma, Wuppertal, Germany.
FAU - Frey, Reiner
AU  - Frey R
AD  - Clinical Pharmacology, Pharma Research Center, Bayer Pharma, Wuppertal, Germany.
FAU - Unger, Sigrun
AU  - Unger S
AD  - Global Biostatistics, Pharma Research Center, Bayer Pharma, Wuppertal, Germany.
FAU - Artmeier-Brandt, Ulrike
AU  - Artmeier-Brandt U
AD  - Clinical Pharmacology, Pharma Research Center, Bayer Pharma, Wuppertal, Germany.
FAU - Weimann, Gerrit
AU  - Weimann G
AD  - Clinical Pharmacology, Pharma Research Center, Bayer Pharma, Wuppertal, Germany.
FAU - Muck, Wolfgang
AU  - Muck W
AD  - Clinical Pharmacology, Pharma Research Center, Bayer Pharma, Wuppertal, Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pulm Circ
JT  - Pulmonary circulation
JID - 101557243
PMC - PMC4860530
OTO - NOTNLM
OT  - NO signaling
OT  - chronic thromboembolic pulmonary hypertension
OT  - pharmacokinetics
OT  - pulmonary arterial hypertension
OT  - soluble guanylate cyclase
EDAT- 2016/05/11 06:00
MHDA- 2016/05/11 06:01
PMCR- 2016/03/01
CRDT- 2016/05/11 06:00
PHST- 2016/05/11 06:00 [entrez]
PHST- 2016/05/11 06:00 [pubmed]
PHST- 2016/05/11 06:01 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - PC2013230 [pii]
AID - 10.1086/682228 [doi]
PST - ppublish
SO  - Pulm Circ. 2016 Mar;6(Suppl 1):S43-8. doi: 10.1086/682228.