Effect of erythromycin on the absorption of fexofenadine in the jejunum, ileum and colon determined using local intubation in healthy volunteers.
OBJECTIVE
To investigate the in vivo intestinal absorption mechanism(s) and systemic availability of fexofenadine in the jejunum, ileum and colon in humans.


METHODS
A single dose of fexofenadine hydrochloride (60 mg as solution) was applied under fasting conditions, either alone or directly after a solution of erythromycin lactobionate (corresponding to a dose of 250 mg erythromycin), to the jejunum, ileum and colon in 6 healthy volunteers (3 male and 3 female) using a regional intubation dosing technology (Bioperm AB, Lund, Sweden). A total of 36 fexofenadine administrations were performed. The administration of fexofenadine to the specified location either alone or in combination with erythromycin was conducted in a randomized manner on 2 consecutive days with a 5-day washout period between doses.


RESULTS
The plasma AUC for fexofenadine (mean +/- SEM) was higher (2.7-to 2.3-fold, p < 0.001) after application to the jejunum (1090 +/- 134 h x ng/ml) than to the ileum (404 +/- 102 h x ng/ml) or colon (476 +/- 212 h x ng/ml). No significant differences were found between application to the ileum and colon. The administration of erythromycin affected the absorption rate after jejunal application with a prolonged tmax from a median of 40 min (range 10-90 min) to a median of 3 hours (range 10-180 min) (p = 0.009). A change in tmax was not observed with application to the ileum and colon. The concomitant administration of erythromycin in the jejunum tended to increase the plasma AUC of fexofenadine from 1090 +/- 134 to 1750 +/- 305 h x ng/ml (p = 0.069).


CONCLUSIONS
The systemic availability of fexofenadine was significantly higher after jejunal administration in accordance with a low permeability compound. The effects of erythromycin suggest that absorption of fexofenadine involves an uptake transport in addition to passive diffusion in the jejunum and predominantly passive diffusion in the ileum and colon.
Petri
N
N
Department of Pharmacy, Biopharmaceutics Research Group Uppsala University, Uppsala, Sweden.
Borga
O
O
Nyberg
L
L
Hedeland
M
M
Bondesson
U
U
Lennernas
H
H
D000284:Administration, Oral; D000328:Adult; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D003106:Colon / Q000378:metabolism; D004357:Drug Synergism; D004917:Erythromycin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007440:Intubation / Q000379:methods*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D020959:Polyethylene; D012016:Reference Values; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D013997:Time Factors
D018926:Anti-Allergic Agents; D000900:Anti-Bacterial Agents; D002214:Capsules; D004917:Erythromycin; D016593:Terfenadine; D020959:Polyethylene; C093230:fexofenadine