Nwokolo C U, Smith J T, Gavey C, Sawyerr A, Pounder R E
Academic Department of Medicine, Royal Free Hospital School of Medicine, London, UK.
Aliment Pharmacol Ther. 1990;4 Suppl 1:29-45.
Twenty-four-hour intragastric acidity and 24-h plasma gastrin concentration were measured on four occasions in six groups of eight healthy male subjects. Each group was studied before dosing, and on days 1, 15 and 29 of dosing with a standard regimen of an H2-receptor antagonist (cimetidine 800 mg nocte, nizatidine 300 mg nocte, famotidine 40 mg nocte, ranitidine 150 mg nocte, ranitidine 150 mg b.d., or ranitidine 300 mg nocte). On the first day of dosing, each regimen using an H2-antagonist caused a significant decrease of intragastric acidity and a significant rise of plasma gastrin concentration. Continued dosing with each H2-antagonist resulted in a significant attenuation of the effect on intragastric acidity, which was most noticeable overnight, but no significant change of plasma gastrin concentration. When grouped together, median integrated nocturnal acidity for the 48 subjects was 485, 35, 67 and 117 mmol.h/L for days 0, 1, 15 and 29, respectively, associated with a median nocturnal integrated plasma gastrin concentration of 46, 72, 79 and 73 pmol.h/L. The study demonstrates that a degree of tolerance develops during continued dosing with all available H2-receptor antagonists, and that this phenomenon occurs during sustained elevation of plasma gastrin concentration.
在六组每组八名健康男性受试者中，分四次测量了24小时胃内酸度和24小时血浆胃泌素浓度。每组在给药前以及使用H2受体拮抗剂标准方案给药的第1天、第15天和第29天进行研究（西咪替丁800mg每晚一次、尼扎替丁300mg每晚一次、法莫替丁40mg每晚一次、雷尼替丁150mg每晚一次、雷尼替丁150mg每日两次或雷尼替丁300mg每晚一次）。在给药的第一天，每种使用H2拮抗剂的方案都会导致胃内酸度显著降低以及血浆胃泌素浓度显著升高。继续使用每种H2拮抗剂给药会导致对胃内酸度的影响显著减弱，这在夜间最为明显，但血浆胃泌素浓度没有显著变化。将48名受试者的数据汇总后，第0天、第1天、第15天和第29天的夜间综合酸度中位数分别为485、35、67和117mmol·h/L，与之相关的夜间血浆胃泌素浓度中位数分别为46、72、79和73pmol·h/L。该研究表明，在持续使用所有可用的H2受体拮抗剂给药期间会产生一定程度的耐受性，并且这种现象发生在血浆胃泌素浓度持续升高期间。
