Parsons M E
Biosciences Division, University of Hertfordshire, Hatfield, UK.
Eur J Gastroenterol Hepatol. 1996 Oct;8 Suppl 1:S15-20. doi: 10.1097/00042737-199610001-00004.
MECHANISM OF ACTION OF PANTOPRAZOLE: Pantoprazole, a new proton-pump inhibitor, is a drug which demonstrates precision from the molecular level to the patient. Like other H+, K(+)-ATPase inhibitors it has in-built selectivity because it accumulates in the acidic compartment of the parietal cell and has to be acid-activated before it acts on the proton pump.
Pantoprazole is chemically more stable than the other proton-pump inhibitors, particularly at near neutral pH, and therefore is unlikely to interact with thiol-containing proteins outside the parietal cell. This acid stability may also account for its highly selective binding to the two cysteine groups located in the proton-pumping pathway of the enzyme.
Pantoprazole is characterized by a degree of pharmacokinetic precision not associated with the other drugs. It shows linear kinetics after oral and intravenous administration. It has a high and constant bioavailability (approximately 77%) which does not change on multiple dosing, so that maximum blood levels are achieved after the first dose. Bioavailability is not altered by concomitant antacid administration, and dose adjustment is not required in elderly patients or those with chronic renal impairment. Extensive studies in man have found no interaction with other drugs. Because of this pharmacokinetic profile, a standard doses of 40 mg is optimal and can be used with confidence in subgroups of patients to give a predictable therapeutic effect.
泮托拉唑的作用机制：泮托拉唑是一种新型质子泵抑制剂，是一种从分子水平到患者均表现出精准性的药物。与其他H⁺，K⁺-ATP酶抑制剂一样，它具有内在选择性，因为它在壁细胞的酸性区室中蓄积，并且在作用于质子泵之前必须被酸激活。
泮托拉唑在化学性质上比其他质子泵抑制剂更稳定，尤其是在接近中性pH值时，因此不太可能与壁细胞外含硫醇的蛋白质相互作用。这种酸稳定性也可能解释了它与位于该酶质子泵途径中的两个半胱氨酸基团的高度选择性结合。
泮托拉唑具有一定程度的药代动力学精准性，这是其他药物所没有的。口服和静脉给药后呈线性动力学。它具有高且恒定的生物利用度（约77%），多次给药时不会改变，因此首次给药后即可达到最高血药浓度。同时服用抗酸剂不会改变生物利用度，老年患者或慢性肾功能损害患者无需调整剂量。在人体进行的广泛研究未发现与其他药物有相互作用。由于这种药代动力学特征，40毫克的标准剂量是最佳的，可放心用于患者亚组以产生可预测的治疗效果。
