Lafutidine prevents low-dose aspirin and loxoprofen induced gastric injury: a randomized, double-blinded, placebo controlled study.
OBJECTIVE
The concomitant use of non-steroidal anti-inflammatory drugs is a risk factor for low-dose aspirin (LDA)-associated upper gastrointestinal toxicity. Lafutidine is an H2-receptor antagonist with gastroprotective activity, produced by acting on capsaicin-sensitive afferent neurons. To evaluate the preventive effect of lafutidine on gastric damage caused by LDA alone and by the combination of both LDA and loxoprofen, we conducted a clinical study using healthy volunteers.


METHODS
A randomized, double-blinded, placebo-controlled, crossover study was carried out. Sixteen healthy volunteers without Helicobacter pylori infection were randomly assigned to two groups. Both groups received 81 mg of aspirin once daily for 14 days (on days 1 to 14) and 60 mg of loxoprofen three times daily for the last 7 days (on days 8 to 14). Placebo or 10 mg of lafutidine was administered twice daily for 14 days in each group. After a 2-week washout period, placebo and lafutidine were crossed over. Endoscopic findings of gastric mucosal damage were evaluated according to the modified Lanza score.


RESULTS
The mean modified Lanza score was 2.19 ± 1.06 (SD) for aspirin plus placebo as compared with 0.50 ± 0.77 for aspirin plus lafutidine (P < 0.001), and 3.00 ± 1.56 for aspirin plus loxoprofen and placebo as compared with 1.25 ± 1.37 for aspirin plus loxoprofen and lafutidine (P < 0.01).


CONCLUSIONS
The addition of loxoprofen to LDA increases gastric mucosal damage. Standard-dose lafutidine significantly prevents gastric mucosal damage induced by LDA alone or LDA plus loxoprofen in H. pylori-negative volunteers. Larger controlled studies are needed to strengthen these findings.
Kato
Mototsugu
M
Division of Endoscopy, Hokkaido University Hospital, Sapporo, Japan. m-kato@med.hokudai.ac.jp
Kamada
Go
G
Yamamoto
Keiko
K
Nishida
Urara
U
Imai
Aki
A
Yoshida
Takeshi
T
Ono
Shouko
S
Nakagawa
Manabu
M
Nakagawa
Soichi
S
Shimizu
Yuichi
Y
Asaka
Masahiro
M
D000081:Acetamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010666:Phenylpropionates / Q000008:administration & dosage / Q000009:adverse effects*; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome; D055815:Young Adult
D000081:Acetamides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006635:Histamine H2 Antagonists; D010666:Phenylpropionates; D010880:Piperidines; D011725:Pyridines; C040656:loxoprofen; C076948:lafutidine; D001241:Aspirin