Miller Ann K, DiCicco Robert A, Freed Martin I
GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA.
Clin Ther. 2002 Jul;24(7):1062-71. doi: 10.1016/s0149-2918(02)80019-4.
Rosiglitazone is an insulin-sensitizing oral agent in the thiazolidinedione class used to treat patients with type 2 diabetes mellitus. It binds to peroxisome proliferator-activated receptor gamma in liver, muscle, and adipose tissue. Ranitidine, a histamine2-receptor antagonist, may be prescribed for patients with type 2 diabetes and esophageal symptoms such as heartburn. By raising gastrointestinal pH levels, ranitidine may affect the bioavailability of coadministered drugs.
This article presents the absolute bioavailability of rosiglitazone, as well as the effects of ranitidine on the pharmacokinetics of rosiglitazone.
Healthy men were enrolled in a randomized, open-label, 4-period, period-balanced crossover study of rosiglitazone and ranitidine. All individuals received each of 4 regimens successively, separated by a 4-day washout period: a single IV dose of rosiglitazone 2 mg administered alone over 1 hour; a single IV dose of rosiglitazone 2 mg administered over 1 hour on the fourth day of treatment with oral ranitidine 150 mg given every 12 hours; a single oral dose of rosiglitazone 4 mg alone; and a single oral dose of rosiglitazone 4 mg on the fourth day of treatment with oral ranitidine 150 mg given every 12 hours. The primary end point was dose-normalized area under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)). Maximum observed plasma concentration (Cmax), the time at which Cmax occurred (Tmax), plasma clearance (CL), steady-state volume of distribution (Vss), and terminal elimination half-life (t 1/2) were also assessed.
Twelve individuals were enrolled. The absolute bioavailability of rosiglitazone was 99%. For AUC(0-infinity), the point estimate and the associated 95% CI for the ratio of ranitidine + IV rosiglitazone to IV rosiglitazone alone was 1.02 (range, 0.88-1.20). With oral rosiglitazone, the AUC(0-infinity) point estimate (95% CI) for the ratio of ranitidine + rosiglitazone to rosiglitazone alone was 0.99 (range, 0.85-1.16). Cmax, Tmax, t 1/2, Vss and CL of rosiglitazone, whether administered orally or intravenously, were unaffected by ranitidine. Oral and IV rosiglitazone were associated with a favorable safety profile and were well tolerated with or without concurrent ranitidine treatment.
In this study of 12 healthy adult male volunteers, the absolute bioavailability of rosiglitazone was 99%, and the oral and IV single-dose pharmacokinetics of rosiglitazone were unaltered by concurrent treatment with ranitidine.
罗格列酮是一种噻唑烷二酮类胰岛素增敏口服药物，用于治疗2型糖尿病患者。它与肝脏、肌肉和脂肪组织中的过氧化物酶体增殖物激活受体γ结合。雷尼替丁是一种组胺2受体拮抗剂，可用于患有2型糖尿病和烧心等食管症状的患者。通过提高胃肠道pH值，雷尼替丁可能会影响同时服用药物的生物利用度。
本文介绍了罗格列酮的绝对生物利用度，以及雷尼替丁对罗格列酮药代动力学的影响。
健康男性参与了一项关于罗格列酮和雷尼替丁的随机、开放标签、4期、周期均衡交叉研究。所有个体依次接受4种治疗方案，各方案之间间隔4天的洗脱期：静脉注射单剂量2mg罗格列酮，1小时内给药完毕；在口服雷尼替丁150mg每12小时一次的治疗第4天，静脉注射单剂量2mg罗格列酮，1小时内给药完毕；口服单剂量4mg罗格列酮；在口服雷尼替丁150mg每12小时一次的治疗第4天，口服单剂量4mg罗格列酮。主要终点是从时间0至无穷大的血浆浓度-时间曲线下剂量标准化面积（AUC(0-∞)）。还评估了最大观察血浆浓度（Cmax）、Cmax出现的时间（Tmax）、血浆清除率（CL）、稳态分布容积（Vss）和末端消除半衰期（t 1/2）。
共纳入12名个体。罗格列酮的绝对生物利用度为99%。对于AUC(0-∞)，雷尼替丁+静脉注射罗格列酮与单独静脉注射罗格列酮的比值的点估计值及相关95%置信区间为1.02（范围为0.88-1.20）。对于口服罗格列酮，雷尼替丁+罗格列酮与单独罗格列酮的比值的AUC(0-∞)点估计值（95%置信区间）为0.99（范围为0.85-1.16）。罗格列酮的Cmax、Tmax、t 1/2、Vss和CL，无论口服还是静脉注射，均不受雷尼替丁影响。口服和静脉注射罗格列酮均具有良好的安全性，无论是否同时进行雷尼替丁治疗，耐受性均良好。
在这项针对12名健康成年男性志愿者的研究中，罗格列酮的绝对生物利用度为99%，雷尼替丁同时治疗未改变罗格列酮的口服和静脉注射单剂量药代动力学。
