Giannini E, Romagnoli P, Fasoli A, Chiarbonello B, Malfatti F, Botta F, Risso D, Lantieri P B, Savarino V, Testa R
Department of Internal Medicine and Health Sciences, University of Genoa, Italy.
Am J Gastroenterol. 2000 Oct;95(10):2762-7. doi: 10.1111/j.1572-0241.2000.03184.x.
Proton pump inhibitors and antimicrobial agents are widely used to eradicate Helicobacter pylori (H. pylori) infection. In the general population the prevalence of infection and of polypharmacy increases the possibility of drug-drug interactions during H. pylori eradication therapy. The purpose of the present study was to assess the prevalence, degree, and clinical relevance of metabolic interference with the cytochrome P450 enzymatic system occurring during 1 wk of administration of omeprazole, lansoprazole, or pantoprazole followed by the association of clarithromycin and metronidazole for another week. The 13C aminopyrine breath test (ABT) was chosen to screen for possible interactions.
We studied 30 patients referred to our Unit for H. pylori eradication therapy. They were randomized to receive either omeprazole (20 mg b.i.d.), lansoprazole (30 mg b.i.d.), or pantoprazole (40 mg b.i.d.) for 2 wk. During the second week clarithromycin (250 mg b.i.d.) and metronidazole (500 mg b.i.d.) were added. ABT was performed before, and at the end of the first and second week of therapy. Percentage of the administered dose of 13C recovered per hour at the peak (percent 13C dose/h at the peak) and cumulative percentage of administered dose of 13C recovered over time at 120 min (percent 13C dose cum120) were the ABT evaluated parameters.
At baseline all patients showed a normal liver function. In individual patients during treatment we observed various liver metabolic interactions both as inhibition and induction, as well as after the first and the second week of therapy. However, mean modifications of the ABT parameters during the 2 weeks of therapy were not statistically significant compared to baseline values. None of the patients who had ABT variations complained of side effects.
H. pylori eradication therapy interferes with cytochrome P450-dependent liver metabolic activity. However, the clinical relevance of these metabolic interactions is not yet apparent, and further investigation is needed. H. pylori eradication therapy appears safe, but these interactions should be considered in the choice of proton pump inhibitor and antimicrobial agents.
质子泵抑制剂和抗菌药物被广泛用于根除幽门螺杆菌（H. pylori）感染。在普通人群中，感染率和联合用药的情况增加了幽门螺杆菌根除治疗期间药物相互作用的可能性。本研究的目的是评估在服用奥美拉唑、兰索拉唑或泮托拉唑1周后，再联合克拉霉素和甲硝唑治疗1周期间，细胞色素P450酶系统代谢干扰的发生率、程度及临床相关性。选用13C氨基比林呼气试验（ABT）来筛查可能的相互作用。
我们研究了30例因幽门螺杆菌根除治疗前来我科就诊的患者。他们被随机分为三组，分别接受奥美拉唑（20 mg，每日两次）、兰索拉唑（30 mg，每日两次）或泮托拉唑（40 mg，每日两次）治疗2周。在第二周添加克拉霉素（250 mg，每日两次）和甲硝唑（500 mg，每日两次）。在治疗的第一周和第二周开始前及结束时进行ABT。ABT评估参数包括峰值时每小时回收的13C给药剂量百分比（峰值时13C剂量/小时百分比）和120分钟时随时间回收的13C给药剂量累积百分比（120分钟时13C剂量累积百分比）。
基线时所有患者肝功能均正常。在治疗期间，我们在个别患者中观察到了各种肝脏代谢相互作用，包括抑制和诱导，以及在治疗的第一周和第二周之后。然而，与基线值相比，治疗2周期间ABT参数的平均变化无统计学意义。ABT有变化的患者均未抱怨有副作用。
幽门螺杆菌根除治疗会干扰细胞色素P450依赖的肝脏代谢活性。然而，这些代谢相互作用的临床相关性尚不明显，需要进一步研究。幽门螺杆菌根除治疗似乎是安全的，但在选择质子泵抑制剂和抗菌药物时应考虑这些相互作用。
