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.
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.


CONCLUSIONS
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.
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
Y
Y
Wu
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
L
L
Ding
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
N-Y
NY
Huang
Department of Pharmacy, The First Affiliated Hospital of the Fourth Military Medical University of PLA, Xi'an, China.
A-D
AD
Wen
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
B
B
Liu
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
W-B
WB
Li
D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001729:Bismuth / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005215:Fasting / Q000097:blood; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets; D013752:Tetracycline / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013607:Tablets; D008795:Metronidazole; C033301:bismuth oxide; D013752:Tetracycline; D001729:Bismuth