Reduced metabolic activity of gut microbiota by antibiotics can potentiate the antithrombotic effect of aspirin.
In this study, we investigated the effects of antibiotics on the pharmacological effects of aspirin. The antithrombotic activity of aspirin was evaluated after antibiotic treatment using tail bleeding assay. The pyrosequencing analysis and selective medium culture assay were performed to investigate the alterations in gut microbiota. In addition, the in vitro metabolism assay with fecal suspension and in vivo pharmacokinetic experiments with antibiotic treatment were conducted. Ampicillin treatment significantly prolonged the bleeding time in aspirin-dosed rats. Oral administration of ampicillin significantly reduced gut microbial aspirin-metabolizing activity by 67.0% in rats. Furthermore, systemic exposure to aspirin and its primary metabolite (M1) was significantly increased in ampicillin-treated rats. The results from the pyrosequencing and selective medium culture with rat fecal samples revealed that ampicillin treatment led to the changes of the amounts and composition profile of gut microbiota. These findings suggest that co-administration of antibiotics can modulate the metabolism and pharmacokinetics of aspirin via suppression of metabolic activity of gut microbiota, which could potentiate the therapeutic potency of aspirin.
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do 426-791, Republic of Korea.
In Sook
IS
Kim
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Dae-Hyeong
DH
Yoo
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Il-Hoon
IH
Jung
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Sumin
S
Lim
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea.
Jin-Ju
JJ
Jeong
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do 426-791, Republic of Korea.
Kyeong-A
KA
Kim
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do 426-791, Republic of Korea.
Ok-Nam
ON
Bae
Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do 426-791, Republic of Korea. Electronic address: yoohh@hanyang.ac.kr.
Hye Hyun
HH
Yoo
Department of Life and Nanopharmaceutical Sciences and Department of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea. Electronic address: dhkim@khu.ac.kr.
Dong-Hyun
DH
Kim
D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D005243:Feces; D005260:Female; D005343:Fibrinolytic Agents / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D055815:Young Adult
D000900:Anti-Bacterial Agents; D005343:Fibrinolytic Agents; D002265:Carboxylic Ester Hydrolases; D001241:Aspirin
Antibiotics; Antithrombotic effect; Aspirin; Gut microbiota; Metabolism