Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 7, 2006; 12(17): 2742-2748
Published online May 7, 2006. doi: 10.3748/wjg.v12.i17.2742
Pharmacokinetics and bioequivalence of ranitidine and bismuth derived from two compound preparations
Quan Zhou, Zou-Rong Ruan, Hong Yuan, Bo Jiang, Dong-Hang Xu
Quan Zhou, Zou-Rong Ruan, Hong Yuan, Bo Jiang, Dong-Hang Xu, Department of Clinical Pharmacology, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China
Correspondence to: Associate Professor, Quan Zhou, Division of Clinical Pharmacology, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China. zhouquan142602@zju.edu.cn
Telephone: +86-571-87783891 Fax: +86-571-87213864
Received: December 12, 2005
Revised: December 20, 2005
Accepted: January 14, 2006
Published online: May 7, 2006
Abstract

AIM: To evaluate the bioequivalence of ranitidine and bismuth derived from two compound preparations.

METHODS: The bioavailability was measured in 20 healthy male Chinese volunteers following a single oral dose (equivalent to 200 mg of ranitidine and 220 mg of bismuth) of the test or reference products in the fasting state. Then blood samples were collected for 24 h. Plasma concentrations of ranitidine and bismuth were analyzed by high-performance liquid chromatography and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. The non-compartmental method was used for pharmacokinetic analysis. Log-transformed Cmax, AUC(0-t) and AUC(0-∞) were tested for bioequivalence using ANOVA and Schuirmann two-one sided t-test. Tmax was analyzed by Wilcoxon’s test.

RESULTS: Various pharmacokinetic parameters of ranitidine derived from the two compound preparations, including Cmax, AUC(0-t), AUC(0-∞), Tmax and T1/2, were nearly consistent with previous observations. These parameters derived from test and reference drug were as follows: Cmax (0.67 ± 0.21 vs 0.68 ± 0.22 mg/L), AUC(0-t) (3.1 ± 0.6 vs 3.0 ± 0.7 mg/L per hour), AUC(0-∞) (3.3 ± 0.6 vs 3.2 ± 0.8 mg/L per hour), Tmax (2.3 ± 0.9 vs 2.1 ± 0.9 h) and T1/2 (2.8 ± 0.3 vs 3.1 ± 0.4 h). In addition, double-peak absorption profiles of ranitidine were found in some Chinese volunteers. For bismuth, those parameters derived from test and reference drug were as follows: Cmax (11.80 ± 7.36 vs 11.40 ± 6.55 μg/L), AUC(0-t) (46.65 ± 16.97 vs 47.03 ± 21.49 μg/L per hour), Tmax (0.50 ± 0.20 vs 0.50 ± 0.20 h) and T1/2 (10.2 ± 2.3 vs 13.0 ± 6.9 h). Ninety percent of confidence intervals for the test/reference ratio of Cmax, AUC(0-t) and AUC(0-) derived from both ranitidine and bismuth were found within the bioequivalence acceptable range of 80%-125%. No significant difference was found in Tmax derived from both ranitidine and bismuth.

CONCLUSION: The two compound preparations are bioequivalent and may be prescribed interchangeably.

Keywords: Ranitidine; Bismuth; Compound preparation; Bioequivalence; Pharmacokinetics; Healthy volunteers; High-performanace liquid chromatography; Inductively coupled plasma-mass spectrometry