Goddard A F, Erah P O, Barrett D A, Shaw P N, Spiller R C
Division of Gastroenterology, University Hospital, Nottingham, UK.
J Antimicrob Chemother. 1998 Feb;41(2):231-6. doi: 10.1093/jac/41.2.231.
Delivery of amoxycillin across the human gastric mucosa to Helicobacter pylori is poor compared with that of metronidazole and clarithromycin, limiting the clinical effectiveness of this penicillin. To investigate the physicochemical properties of penicillins that influence their flux across gastric mucosa, the fluxes of metronidazole and eight penicillins were measured in vitro across rat gastric mucosa. The lipophilicity of these drugs was also measured using potentiometric titration. The mean fluxes of monobasic penicillins (range 0.66-0.89 nmol/cm2/h) were significantly lower than those of the aminopenicillins (range 1.94-2.80 nmol/cm2/h) (P < 0.005). Penicillin flux was not significantly correlated with lipophilicity as measured, but was significantly correlated with published protein binding data (rs = 0.9048, P < 0.002). Metronidazole flux was significantly higher than that of any penicillin at 22.6 (+/-0.9) nmol/cm2/h (P < 0.001). Therefore, the in-vitro gastric delivery of penicillins can be predicted from protein binding which may in turn predict activity against H. pylori in vivo.
与甲硝唑和克拉霉素相比，阿莫西林透过人胃黏膜到达幽门螺杆菌的能力较差，这限制了这种青霉素的临床疗效。为了研究影响青霉素透过胃黏膜通量的物理化学性质，在体外测量了甲硝唑和8种青霉素透过大鼠胃黏膜的通量。还使用电位滴定法测量了这些药物的亲脂性。一元青霉素的平均通量（范围为0.66 - 0.89 nmol/cm²/h）显著低于氨基青霉素（范围为1.94 - 2.80 nmol/cm²/h）（P < 0.005）。所测青霉素通量与亲脂性无显著相关性，但与已发表的蛋白结合数据显著相关（rs = 0.9048，P < 0.002）。甲硝唑通量在22.6（±0.9）nmol/cm²/h时显著高于任何一种青霉素（P < 0.001）。因此，青霉素的体外胃内递送可通过蛋白结合来预测，而蛋白结合反过来可能预测其体内对幽门螺杆菌的活性。
