在健康志愿者中使用局部插管法测定红霉素对非索非那定在空肠、回肠和结肠吸收的影响。

Effect of erythromycin on the absorption of fexofenadine in the jejunum, ileum and colon determined using local intubation in healthy volunteers.

作者信息

Petri N, Borga O, Nyberg L, Hedeland M, Bondesson U, Lennernas H

机构信息

Department of Pharmacy, Biopharmaceutics Research Group Uppsala University, Uppsala, Sweden.

出版信息

Int J Clin Pharmacol Ther. 2006 Feb;44(2):71-9. doi: 10.5414/cpp44071.

DOI:10.5414/cpp44071

PMID:16502766

Abstract

OBJECTIVE

To investigate the in vivo intestinal absorption mechanism(s) and systemic availability of fexofenadine in the jejunum, ileum and colon in humans.

METHOD

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.

摘要

目的

研究非索非那定在人体空肠、回肠和结肠中的体内肠道吸收机制及全身可用性。

方法

在禁食条件下，采用区域插管给药技术（瑞典隆德的Bioperm AB公司），将单剂量的盐酸非索非那定（60mg溶液）单独或在乳糖酸红霉素溶液（相当于250mg红霉素剂量）之后，给予6名健康志愿者（3男3女）的空肠、回肠和结肠。共进行了36次非索非那定给药。将非索非那定单独或与红霉素联合给药至指定部位，在连续2天以随机方式进行，剂量之间有5天的洗脱期。

结果

非索非那定的血浆AUC（平均值±标准误）在给予空肠后（1090±134h×ng/ml）高于回肠（404±102h×ng/ml）或结肠（476±212h×ng/ml）（2.7至2.3倍，p<0.001）。回肠和结肠给药之间未发现显著差异。红霉素给药影响空肠给药后的吸收速率，tmax从中位数40分钟（范围10至90分钟）延长至中位数3小时（范围10至180分钟）（p = 0.009）。回肠和结肠给药未观察到tmax变化。空肠中同时给予红霉素倾向于将非索非那定的血浆AUC从1090±134增加至1750±305h×ng/ml（p = 0.069）。