Pharmacokinetics and bioequivalence of ranitidine and bismuth derived from two compound preparations.
OBJECTIVE
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 C(max), AUC( (0-t) ) and AUC( (0-infinity) ) were tested for bioequivalence using ANOVA and Schuirmann two-one sided t-test. T(max) was analyzed by Wilcoxon's test.


RESULTS
Various pharmacokinetic parameters of ranitidine derived from the two compound preparations, including C(max), AUC( (0-t)), AUC( (0-infinity)), T(max) and T((1/2)), were nearly consistent with previous observations. These parameters derived from test and reference drug were as follows: C(max) (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-infinity) ) (3.3 +/- 0.6 vs 3.2 +/- 0.8 mg/L per hour), T(max) (2.3 +/- 0.9 vs 2.1 +/- 0.9 h) and T((1/2)) (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: C(max) (11.80 +/- 7.36 vs 11.40 +/- 6.55 microg/L), AUC( (0-t) ) (46.65 +/- 16.97 vs 47.03 +/- 21.49 microg/L per hour), T(max) (0.50 +/- 0.20 vs 0.50 +/- 0.20 h) and T((1/2)) (10.2 +/- 2.3 vs 13.0 +/- 6.9 h). Ninety percent of confidence intervals for the test/reference ratio of C(max), AUC( (0-t) ) and AUC( (0-infinity) ) derived from both ranitidine and bismuth were found within the bioequivalence acceptable range of 80%-125%. No significant difference was found in T(max) derived from both ranitidine and bismuth.


CONCLUSIONS
The two compound preparations are bioequivalent and may be prescribed interchangeably.
Zhou
Quan
Q
Department of Clinical Pharmacology, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang Province, China. zhouquan142602@zju.edu.cn
Ruan
Zou-Rong
ZR
Yuan
Hong
H
Jiang
Bo
B
Xu
Dong-Hang
DH
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000863:Antacids / Q000493:pharmacokinetics*; D001682:Biological Availability; D001729:Bismuth / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006635:Histamine H2 Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D011899:Ranitidine / Q000097:blood / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D013054:Spectrophotometry, Atomic; D013810:Therapeutic Equivalency; D013997:Time Factors
D000863:Antacids; D006635:Histamine H2 Antagonists; D011899:Ranitidine; D001729:Bismuth