McFadyen M L, Folb P I, Miller R, Marks I N, Moshal M G
Eur J Clin Pharmacol. 1983;24(4):441-7. doi: 10.1007/BF00609883.
The pharmacokinetics of orally administered ranitidine were studied in 17 male patients with chronic duodenal ulceration. The patients were divided into 2 groups, 10 responders and 7 nonresponders, on the basis of their endoscopic response to ranitidine treatment. The 10 responders were studied both after a single 150 mg dose (SD) and after multiple dosing (MD) with ranitidine 150 mg twice daily for 4 weeks. The area under the curve (AUC) and maximum concentration (Cmax) were significantly higher (p less than 0.01 and p less than 0.05, respectively) after MD than after SD, but the half-life (t1/2) and minimum concentration (Cmin) 12 h postdosing did not differ. The non-responders were studied after MD only and their pharmacokinetic characteristics were compared with those of responders. No differences between the 2 groups were found. However, 2 non-responders had particularly low plasma ranitidine levels and high acid output. Such patients may need larger doses of ranitidine for adequate suppression of gastric acid. Five patients (4 responders and 1 non-responder) received ranitidine 20 mg i.v. The drug followed a two-compartment model, with mean values for t1/2 beta, volume of distribution steady-state and total plasma clearance of 80 min, 701 and 680 ml/min, respectively. The oral bioavailability of ranitidine in these 5 patients showed wide variation (27-76%; mean 51%).
对17名患有慢性十二指肠溃疡的男性患者研究了口服雷尼替丁的药代动力学。根据患者对雷尼替丁治疗的内镜反应,将患者分为两组,10名反应者和7名无反应者。对10名反应者分别进行了单次150mg剂量(SD)给药后以及雷尼替丁150mg每日两次、连续4周多次给药(MD)后的研究。多次给药后的曲线下面积(AUC)和最大浓度(Cmax)显著高于单次给药后(分别为p<0.01和p<0.05),但半衰期(t1/2)和给药后12小时的最低浓度(Cmin)无差异。仅对无反应者进行了多次给药后的研究,并将其药代动力学特征与反应者进行了比较。两组之间未发现差异。然而,2名无反应者的血浆雷尼替丁水平特别低且胃酸分泌高。此类患者可能需要更大剂量的雷尼替丁以充分抑制胃酸。5名患者(4名反应者和1名无反应者)静脉注射了20mg雷尼替丁。该药物遵循二室模型,t1/2β、稳态分布容积和总血浆清除率的平均值分别为80分钟、701和680ml/分钟。这5名患者中雷尼替丁的口服生物利用度差异很大(27%-76%;平均51%)。