title: Effects of one-time apple juice ingestion on the pharmacokinetics of fexofenadine enantiomers.
abstract: OBJECTIVE
  We examined the effect of a single apple juice intake on the pharmacokinetics of fexofenadine enantiomers in healthy Japanese subjects.
  
  
  METHODS
  In a randomized two phase, open-label crossover study, 14 subjects received 60 mg of racemic fexofenadine simultaneously with water or apple juice. For the uptake studies, oocytes expressing organic anion-transporting polypeptide 2B1 (OATP2B1) were incubated with 100 μM (R)- and (S)-fexofenadine in the presence or absence of 10 % apple juice.
  
  
  RESULTS
  One-time ingestion of apple juice significantly decreased the area under the plasma concentration-time curve (AUC0-24) for (R)- and (S)-fexofenadine by 49 and 59 %, respectively, and prolonged the time to reach the maximum plasma concentration (t max) of both enantiomers (P < 0.001). Although apple juice greatly reduced the amount of (R)- and (S)-fexofenadine excretion into urine (Ae0-24) by 54 and 58 %, respectively, the renal clearances of both enantiomers were unchanged between the control and apple juice phases. For in vitro uptake studies, the uptake of both fexofenadine enantiomers into OATP2B1 complementary RNA (cRNA)-injected oocytes was significantly higher than that into water-injected oocytes, and this effect was greater for (R)-fexofenadine. In addition, apple juice significantly decreased the uptake of both enantiomers into OATP2B1 cRNA-injected oocytes.
  
  
  CONCLUSIONS
  These results suggest that OATP2B1 plays an important role in the stereoselective pharmacokinetics of fexofenadine and that one-time apple juice ingestion probably inhibits intestinal OATP2B1-mediated transport of both enantiomers. In addition, this study demonstrates that the OATP2B1 inhibition effect does not require repeated ingestion or a large volume of apple juice.
authors.affiliation: Department of Hospital Pharmacy, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Akamine
authors.forename: Masatomo
authors.initials: M
authors.lastname: Miura
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Komori
authors.forename: Shun
authors.initials: S
authors.lastname: Saito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kusuhara
authors.forename: Ikumi
authors.initials: I
authors.lastname: Tamai
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ieiri
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Uno
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
mesh_terms: D000328:Adult; D000818:Animals; D018926:Anti-Allergic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D019540:Area Under Curve; D001628:Beverages; D018592:Cross-Over Studies; D004435:Eating; D005260:Female; D018565:Food-Drug Interactions; D005638:Fruit; D039563:Histamine H1 Antagonists, Non-Sedating / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D027845:Malus; D009865:Oocytes / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D018075:RNA, Complementary / Q000235:genetics; D013237:Stereoisomerism; D016593:Terfenadine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D014982:Xenopus laevis; D055815:Young Adult
chemical_list: D018926:Anti-Allergic Agents; D039563:Histamine H1 Antagonists, Non-Sedating; D027361:Organic Anion Transporters; D018075:RNA, Complementary; C450859:SLCO2B1 protein, human; D016593:Terfenadine; C093230:fexofenadine