Regårdh C G, Andersson T, Lagerström P O, Lundborg P, Skånberg I
Hässle Research Laboratories, Mölndal, Sweden.
Ther Drug Monit. 1990 Mar;12(2):163-72. doi: 10.1097/00007691-199003000-00010.
The pharmacokinetics of omeprazole, hydroxyomeprazole, omeprazolesulfone, and "remaining metabolites" have been studied in eight young healthy subjects following an acute i.v. and oral dose of 10 and 20 mg of 14C-labeled drug, respectively. The oral dose was given as a buffered solution. Two subjects exhibited essentially higher and more sustained plasma levels of omeprazole than the others. This was due to a higher bioavailability, lower clearance, and longer t1/2 of omeprazole in these two subjects. Maximum concentration (0.7-4.6 mumol/L) was reached between 10 and 25 min after oral dosing. The median bioavailability was 39% (25-117%) and the median systemic plasma clearance was 624 ml/min (range of 59-828 ml/min). The corresponding t1/2 for the i.v. dose was 35 min (16-150 min) and 39 min (14-186 min) after oral administration. The drug was rapidly distributed to extravascular sites (mean t1/2 lambda 1 = 3.0 +/- 0.8 min). Mean Vss was 0.23 +/- 0.04 L/kg. Low systemic clearance of omeprazole was associated with a decreased formation rate of hydroxyomepraxole and "remaining metabolites" while omeprazolesulfone formation seemed to be less affected. However, there was a clear-cut correlation between the t1/2 of omeprazole and of its omeprazolesulfone metabolite, indicating that the elimination of these two compounds is mediated by the same isoenzyme. The mean urinary recovery of the radioactive dose during 96 h was 78.3 +/- 2.3 and 75.7 +/- 2.6% for the i.v. and oral dose, respectively. Insignificant amounts were due to unchanged drug and omeprazolesulfone. The excretion of hydroxyomeprazole during the first 12 h varied between 4.6 to 15.5% of a given dose. The mean recovery of radioactivity in the feces was 19.3 +/- 3.1% of a given i.v. dose and 18.2 +/- 2.3% when given orally. It is concluded that omeprazole is mainly eliminated metabolically and that there is a substantial interindividual variation in the rate of formation of primary and secondary metabolites. This variation in omeprazole disposition is probably of limited clinical importance. The half-life, with a maximum of approximately 3 h, is too short to cause accumulation when the drug is administered in a once-daily regimen.
在8名年轻健康受试者中，分别静脉注射和口服10毫克及20毫克14C标记的奥美拉唑后，对奥美拉唑、羟基奥美拉唑、奥美拉唑砜及“其余代谢产物”的药代动力学进行了研究。口服剂量以缓冲溶液形式给药。两名受试者的奥美拉唑血浆水平明显高于其他受试者，且维持时间更长。这是因为这两名受试者中奥美拉唑的生物利用度更高、清除率更低、半衰期更长。口服给药后10至25分钟达到最大浓度（0.7 - 4.6微摩尔/升）。中位生物利用度为39%（25 - 117%），中位全身血浆清除率为624毫升/分钟（范围为59 - 828毫升/分钟）。静脉注射剂量的相应半衰期为35分钟（16 - 150分钟），口服给药后为39分钟（14 - 186分钟）。药物迅速分布到血管外部位（平均t1/2 lambda 1 = 3.0 +/- 0.8分钟）。平均稳态分布容积为0.23 +/- 0.04升/千克。奥美拉唑的全身清除率较低与羟基奥美拉唑及“其余代谢产物”的生成速率降低有关，而奥美拉唑砜的生成似乎受影响较小。然而，奥美拉唑及其奥美拉唑砜代谢产物的半衰期之间存在明显相关性，表明这两种化合物的消除由同一种同工酶介导。静脉注射和口服剂量在96小时内放射性剂量的平均尿回收率分别为78.3 +/- 2.3%和75.7 +/- 2.6%。少量是由于未变化的药物和奥美拉唑砜。给药后前12小时内羟基奥美拉唑的排泄量在给定剂量的4.6%至15.5%之间变化。粪便中放射性的平均回收率，静脉注射给药时为给定剂量的19.3 +/- 3.1%，口服给药时为18.2 +/- 2.3%。结论是奥美拉唑主要通过代谢消除，且初级和次级代谢产物的生成速率存在个体间显著差异。奥美拉唑处置的这种差异可能在临床上意义有限。半衰期最长约为3小时，当药物每日一次给药时，太短以至于不会引起蓄积。
