Vinayek R, Amantea M A, Maton P N, Frucht H, Gardner J D, Jensen R T
Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Gastroenterology. 1991 Jul;101(1):138-47. doi: 10.1016/0016-5085(91)90470-6.
The pharmacokinetics and pharmacodynamics of oral and IV omeprazole after a single dose were studied in 9 patients with the Zollinger-Ellison syndrome to determine whether the increased dose required to control gastric acid hypersecretion could be explained on the basis of altered pharmacokinetics. Each patient was studied both after receiving a single IV bolus of omeprazole (40 mg) and after receiving a single oral dose of omeprazole (80 mg). Intravenous and oral omeprazole doses were administered 1 week apart. Gastric acid secretion and plasma concentrations of omeprazole after drug administration were determined in each patient. The area under the plasma concentration curve, clearance, and volume of distribution after IV omeprazole administration and the area under the plasma concentration curve, peak plasma concentration, and time required to reach the peak after oral omeprazole administration were not different from those reported previously for normal subjects and patients with peptic ulcer disease. Mean (+/- SEM) bioavailability of oral omeprazole for all patients was 68% +/- 16%, which was similar to the bioavailability reported previously for normal subjects. Three patients had a significantly lower bioavailability reported previously for normal subjects. Three patients had a significantly lower bioavailability (20% +/- 8%) than the others, and their basal acid outputs were significantly higher than those of the other 7 patients. For all patients there was an inverse correlation between bioavailability and basal acid output (r = 0.76; P less than 0.02). The mean (+/- SEM) elimination half-lives of IV and oral omeprazole were not different (2.3 +/- 0.4 vs. 2.4 +/- 0.5 hours) but were significantly longer than those reported previously for normal subjects (P less than 0.02). The duration of action correlated with the elimination half-life of the drug (r = 0.87; P less than 0.003) and area under the plasma concentration curve (r = 0.72; P less than 0.03). The mean durations of action of IV and oral omeprazole were not significantly different (34 +/- 7.2 vs. 35 +/- 6.2 hours). It was concluded that altered pharmacokinetics do not account for the increased drug requirement of omeprazole in patients with the Zollinger-Ellison syndrome. In contrast to a previous study, the oral and IV omeprazole had the same duration of action, suggesting that intermittent bolus administration of parenteral omeprazole will obviate the need for continuous infusion of histamine H2-receptor antagonists in patients requiring parenteral antisecretory drugs. Furthermore, an IV dose every 12 hours controlled acid secretion in all patients, suggesting this as the recommended dose interval in patients requiring parenteral drug therapy.
在9例卓艾综合征患者中研究了单剂量口服和静脉注射奥美拉唑后的药代动力学和药效学，以确定控制胃酸分泌过多所需增加的剂量是否可以基于药代动力学改变来解释。每位患者在接受单次静脉推注奥美拉唑（40mg）后和接受单次口服奥美拉唑（80mg）后均进行了研究。静脉注射和口服奥美拉唑剂量相隔1周给药。测定了每位患者给药后胃酸分泌和血浆中奥美拉唑浓度。静脉注射奥美拉唑后的血浆浓度曲线下面积、清除率和分布容积，以及口服奥美拉唑后的血浆浓度曲线下面积、血浆峰浓度和达到峰浓度所需时间，与先前报道的正常受试者和消化性溃疡病患者并无差异。所有患者口服奥美拉唑的平均（±标准误）生物利用度为68%±16%，与先前报道的正常受试者的生物利用度相似。3例患者的生物利用度明显低于先前报道的正常受试者。3例患者的生物利用度（20%±8%）明显低于其他患者，且其基础酸分泌量明显高于其他7例患者。对于所有患者，生物利用度与基础酸分泌量呈负相关（r = 0.76；P<0.02）。静脉注射和口服奥美拉唑的平均（±标准误）消除半衰期无差异（2.3±0.4对2.4±0.5小时），但明显长于先前报道的正常受试者（P<0.02）。作用持续时间与药物的消除半衰期（r = 0.87；P<0.003）和血浆浓度曲线下面积（r = 0.72；P<0.03）相关。静脉注射和口服奥美拉唑的平均作用持续时间无显著差异（34±7.2对35±6.2小时）。得出的结论是，药代动力学改变不能解释卓艾综合征患者对奥美拉唑药物需求的增加。与先前的一项研究相反，口服和静脉注射奥美拉唑的作用持续时间相同，这表明对于需要胃肠外抗分泌药物的患者，间歇性推注胃肠外奥美拉唑将无需持续输注组胺H2受体拮抗剂。此外，每12小时静脉注射一次剂量可控制所有患者的胃酸分泌，这表明这是需要胃肠外药物治疗患者的推荐剂量间隔。
