title: Gastrointestinal symptoms in idiopathic pulmonary fibrosis patients treated with pirfenidone and herbal medicine.
abstract: Pirfenidone is an antifibrotic agent for patients with pulmonary fibrosis, but this drug has adverse gastrointestinal (GI) effects. The first aim of this study was to assess GI symptoms due to pirfenidone by using a new questionnaire for reflux symptoms and dismotility symptoms. Whether adding herbal medicine of rikkunshi-to improved GI symptoms due to pirfenidone therapy was also investigated. This was a randomized controlled trial performed on 17 IPF patients. The patients were assigned to two groups, and the study period was 8 weeks. The pirfenidone group received pirfenidone therapy for 8 weeks with add-on rikkunshi-to from 4 weeks, while the control group did not receive either of these agents. To assess the effects of RK, plasma levels of acyl-ghrelin and des-acyl-ghrelin, serum KL-6 and surfactant protein-D, and pulmonary function tests were monitored. GI symptoms were most severe during the initial 2 weeks of pirfenidone therapy at a dose of 600 mg/day. Both reflux symptoms and dismotility symptoms deteriorated. Rikkunshi-to improved GI symptoms to the level prior to pirfenidone therapy. Plasma levels of des-acyl-ghrelin and acyl-/des-acyl-ghrelin ratio changed significantly at 8 weeks compared to 2 weeks. GI adverse events due to PFD were most severe in the first 2 weeks of treatment at a dose of 600 mg/day, and both reflux and dismotility symptoms deteriorated, but the drug was well tolerated at 1200 mg/day. Rikkunshi-to contributed to improvement of GI symptoms, but plasma ghrelin levels did not reflect the improvement of GI symptoms.
authors.affiliation: Department of Respiratory Medicine, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimoyama
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawada
authors.affiliation: Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital Gastroenterology, Maebashi, Gunma, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kusano
authors.affiliation: Clinical laboratory Center, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hosomi
authors.affiliation: Clinical laboratory Center, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
authors.affiliation: Department of Respiratory Medicine, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawata
authors.affiliation: Department of Respiratory Medicine, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Horie
authors.affiliation: Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Gunma University School of Health Sciences, Maebashi, Gunma, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Dobashi
authors.affiliation: Department of Respiratory Medicine, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Takise
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005764:Gastroesophageal Reflux / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D054439:Ghrelin / Q000097:blood; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004365:Drugs, Chinese Herbal; D054439:Ghrelin; C060192:MUC1 protein, human; D018396:Mucin-1; D011728:Pyridones; C422650:ghrelin, des-n-octanoyl; C084136:liu-jun-zi-tang; C093844:pirfenidone