Pharmacokinetics of Metronidazole, Tetracycline and Bismuth in Healthy Volunteers after Oral Administration of Compound Tablets Containing a Combination of Metronidazole, Tetracycline Hydrochloride and Bismuth Oxide

Abstract

Background:

To eradicate Helicobacter pylori in human pylorus and to heal duodenal ulcers, recently, a new formulation of combination tablets containing metronidazole 125 mg, tetracycline hydrochloride 125 mg and bismuth oxide 40 mg has been developed.

Objective:

To investigate the pharmacokinetics of metronidazole, tetracycline and bismuth in healthy Chinese volunteers after oral administration of the test formulation.

Methods:

A one-sequence, 3-period study was conducted in 12 Chinese healthy volunteers (6 male, 6 female). Volunteers each received single low dose (1 tablet) under fed condition in period 1, single high dose (3 tablets) under fasted condition in period 2, and single high dose (3 tablets) and multiple doses (3 tablets at once, 4 times daily for 7 consecutive days) under fed condition in period 3. Blood samples were collected and determined over 48 h in every period.

Results and conclusion:

After single high dose administration under fed condition, the C _max of metronidazole, tetracycline and bismuth were 6.833±0.742 μg/mL, 0.8513±0.1253 μg/mL and 3.32±1.89 ng/mL, respectively. The C _max and AUC _0–48 of metronidazole increased in proportion to the doses within the tested dose range, but tetracycline and bismuth did not. Food caused 10% and 80% decrease of the C _max for metronidazole and bismuth, respectively, but did not affect tetracycline. No gender effect was found on the pharmacokinetics of the 3 ingredients. In the steady state, the C _av of metronidazole, tetracycline and bismuth were 20.75±3.52 μg/mL, 1.900±0.243 μg/mL and 5.61±1.34 ng/mL, respectively.

Key words

pharmacokinetics - metronidazole - tetracycline - bismuth - LC-MS/MS - fluorescence

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