title: Changes in gastric pH and in pharmacokinetics of ulipristal acetate - a drug-drug interaction study using the proton pump inhibitor esomeprazole.
abstract: OBJECTIVE
  Ulipristal acetate is a novel selective progesterone receptor modulator for the treatment of benign gynecological conditions such as uterine myoma. As a Biopharmaceutical Classification System (BCS) II compound, it is highly soluble at low pH but has low solubility at neutral conditions. Esomeprazole, a proton pump inhibitor used widely for treatment of gastric and duodenal ulcers, efficiently increases gastric pH. Thus, the aim of this study was to determine the effects of esomeprazole on the pharmacokinetics of ulipristal acetate.
  
  
  METHODS
  This was a nonrandomized, single sequence, 2 period, open, study in 18 healthy female subjects. Subjects received oral ulipristal acetate tablets (10 mg) once on Days 1 and 13 and daily esomeprazole administrations (20 mg) from Days 9 through 14.
  
  
  RESULTS
  Co-administration of esomeprazole decreased geometric mean Cmax of ulipristal acetate by 65% (geometric mean ratio point estimate (90% CI): 0.35 (0.28 - 0.42)), and delayed median tmax from 0.75 to 1.00 h (Hodges-Lehmann estimate of difference (90% CI): tmax 0.63 (0.25 - 1.25)) but had minor effects on AUCs of +15% and +11% (geometric mean ratio point estimates (90% CI): AUC0-t 1.15 (1.02 - 1.31) and AUC0-∞ (1.11 (0.98 - 1.27)), respectively. A total of 6 adverse events were reported by 4 subjects, none of them being serious.
  
  
  CONCLUSIONS
  Concomitant use of ulipristal acetate with esomeprazole at therapeutic concentrations led to a modified absorption rate while exposure in terms of AUC remained close to bioequivalence limits. In the context of chronic administration of ulipristal acetate, no clinically significant effects are expected from co-administration with drugs increasing gastric pH.
authors.affiliation: PregLem SA, Geneva, Switzerland. oliver.pohl@preglem.com
authors.forename: Oliver
authors.initials: O
authors.lastname: Pohl
authors.forename: Ian
authors.initials: I
authors.lastname: Osterloh
authors.forename: Véronique
authors.initials: V
authors.lastname: Lecomte
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gotteland
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D003270:Contraceptive Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D003967:Diarrhea / Q000139:chemically induced; D004347:Drug Interactions; D064098:Esomeprazole / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005750:Gastric Juice / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008875:Middle Aged; D009649:Norpregnadienes / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D012016:Reference Values; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D003270:Contraceptive Agents; D009649:Norpregnadienes; D054328:Proton Pump Inhibitors; D064098:Esomeprazole; C555622:ulipristal acetate