Palovaara Sanna, Tybring Gunnel, Laine Kari
Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland.
Br J Clin Pharmacol. 2003 Aug;56(2):232-7. doi: 10.1046/j.1365-2125.2003.01868.x.
To study the effect of an oral contraceptive (OC) formulation containing ethinyloestradiol and levonorgestrel (LNG) (combination OC) or LNG alone on the CYP2C19-mediated hydroxylation of omeprazole in healthy females.
This was an open crossover study with three phases. In phase one, 10 healthy females received a single 40-mg dose of omeprazole. Thereafter the subjects received in a random order either 40 micro g ethinyloestradiol and 75 micro g LNG or 60 micro g LNG alone once daily for 10 days. On day 10, 1 h after the last OC dose, subjects received a single 40-mg oral dose of omeprazole. The plasma concentrations of omeprazole, 5'-hydroxyomeprazole and omeprazole sulphone were determined for up to 8 h.
The use of combination OC increased the area under the curve (AUC) of omeprazole by 38% [95% confidence interval (CI) - 3.8, 80; P = 0.040] and caused a 48% increase (95% CI 28, 68) in the AUC ratio of omeprazole/5-hydroxyomeprazole. LNG alone did not effect the 5'-hydroxylation of omeprazole. Neither of the OC preparations seemed to have an inhibitory effect on the formation of omeprazole sulphone by CYP3A4.
Oral contraceptives containing ethinyloestradiol but not those containing only LNG decrease CYP2C19 activity.
研究含乙炔雌二醇和左炔诺孕酮（LNG）的口服避孕药（复方口服避孕药）或单独使用LNG对健康女性中奥美拉唑经CYP2C19介导的羟基化作用的影响。
这是一项分为三个阶段的开放交叉研究。在第一阶段，10名健康女性接受单次40毫克剂量的奥美拉唑。此后，受试者随机顺序接受每日一次40微克乙炔雌二醇和75微克LNG或单独60微克LNG，持续10天。在第10天，最后一次口服避孕药剂量后1小时，受试者接受单次40毫克口服剂量的奥美拉唑。测定奥美拉唑、5'-羟基奥美拉唑和奥美拉唑砜的血浆浓度长达8小时。
使用复方口服避孕药使奥美拉唑的曲线下面积（AUC）增加了38%[95%置信区间（CI）-3.8，80；P=0.040]，并使奥美拉唑/5-羟基奥美拉唑的AUC比值增加了48%（95%CI 28，68）。单独使用LNG对奥美拉唑的5'-羟基化没有影响。两种口服避孕药制剂似乎都对CYP3A4介导的奥美拉唑砜形成没有抑制作用。
含乙炔雌二醇的口服避孕药会降低CYP2C19活性，而仅含LNG的口服避孕药则不会。
