Goddard A F, Spiller R C
Division of Gastroenterology, University Hospital, Nottingham, United Kingdom.
Antimicrob Agents Chemother. 1997 Jun;41(6):1246-9. doi: 10.1128/AAC.41.6.1246.
A novel animal model for studying antibiotic transfer across gastric mucosa was developed by using adult rats. Gastric corpus mucosa was mounted in an Ussing chamber system and bathed in oxygenated Krebs solution. Metronidazole flux from serosa to mucosa (J(S-->M)) was measured over 60 min under basal conditions and compared with mucosa-to-serosa flux (J(M-->S)). The effects of varying the chamber cross-sectional diameter and of stimulation by histamine and carbachol were assessed. Metronidazole J(M-->S) was measured with the mucosal pH at 2.2, 2.7, 3.2, and 7.4. Amoxicillin J(S-->M) under basal conditions was also measured and compared with metronidazole J(S-->M). Metronidazole J(S-->M) was proportional to serosal concentration (P < 0.001) under basal conditions, being 3.98 nmol x h(-1) x cm(-2) with a serosal concentration of 0.2 mmol/liter. Amoxicillin J(S-->M) was significantly lower under similar conditions at 0.50 nmol x h(-1) x cm(-2) (P < 0.01). Metronidazole J(S-->M) was not significantly different from J(M-->S), between chambers of different sizes, or following stimulation. When the mucosal pH was changed, J(M-->S) was proportional to the un-ionized concentration on the mucosal side (P < 0.001). Therefore, this model shows properties analogous to those of human gastric mucosa in vivo, with partitioning of metronidazole on the mucosal side according to pH, diffusion of metronidazole across the mucosa in both directions, and selectivity for different antibiotics, and it will be useful for the study of other therapeutic agents in the treatment of Helicobacter pylori.
通过使用成年大鼠，建立了一种用于研究抗生素跨胃黏膜转运的新型动物模型。胃体黏膜被安装在尤斯灌流室系统中，并浸泡在充氧的 Krebs 溶液中。在基础条件下，测量甲硝唑从浆膜到黏膜的通量（J(S→M)），持续 60 分钟，并与从黏膜到浆膜的通量（J(M→S)）进行比较。评估了改变灌流室横截面直径以及组胺和卡巴胆碱刺激的影响。在黏膜 pH 为 2.2、2.7、3.2 和 7.4 时测量甲硝唑 J(M→S)。还测量了基础条件下阿莫西林的 J(S→M)，并与甲硝唑的 J(S→M)进行比较。在基础条件下，甲硝唑 J(S→M)与浆膜浓度成正比（P < 0.001），当浆膜浓度为 0.2 mmol/升时，其值为 3.98 nmol·h⁻¹·cm⁻²。在类似条件下，阿莫西林的 J(S→M)显著较低，为 0.50 nmol·h⁻¹·cm⁻²（P < 0.01）。甲硝唑 J(S→M)在不同大小的灌流室之间或刺激后与 J(M→S)无显著差异。当黏膜 pH 改变时，J(M→S)与黏膜侧的非离子化浓度成正比（P < 0.001）。因此，该模型显示出与体内人胃黏膜类似的特性，甲硝唑在黏膜侧根据 pH 进行分配，在两个方向上跨黏膜扩散，并且对不同抗生素具有选择性，它将有助于研究其他治疗幽门螺杆菌的治疗药物。
