Multicenter, double-blind, randomized comparison of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, and loperamide in adults with acute nonspecific diarrhea.
BACKGROUND
Seirogan, an herbal medication containing wood creosote, a mixture of simple phenolic (single-ring)compounds, has been marketed in Asia for the past century as an antidiarrheal and antispasmodic medication. This was the first randomized, double-blind study of this herbal medication in patients with acute, nonspecific diarrhea.


OBJECTIVE
The aim of this study was to compare the efficacy and tolerability of wood creosote with those of loperamide hydrochloride in patients with acute, nonspecific diarrhea.


METHODS
This double-blind, randomized, active-controlled study was conducted at 12 centers across the United States and Mexico. Patients aged >or=18 years with acute, nonspecific diarrhea, defined as a history of diarrhea for <or=72 hours and passage of >or=3 unformed stools in the 24 hours before the study, accompanied by >or=1 associated symptom (ie, nausea, vomiting, abdominal cramping, and/or fever [<or=101.0 degrees F or <or=38.3 degrees C]), were eligible for the study Patients received wood creosote 135 mg (<or=5 doses/d) or loperamide 4 mg (loading dose) followed by 2 mg (<or=8 mg/d) after each loose stool for <or=3 days. The primary efficacy end point was the time to the last unformed stool (TTLUS). Clinical safety laboratory tests and patient diaries were used to assess tolerability.


RESULTS
One hundred twenty-three patients (74 women, 49 men; mean [SD] age, 42.6 [14.9] years; age range, 18-90 years) were randomized to receive wood creosote (n = 60) or loperamide (n = 63). Eighty-four of the 123 enrolled patients (68.3%) were Hispanic, 18 (14.6%) white, 17 (13.8%) black, and 4 (3.3%) Asian or Pacific Islander. The majority of patients (88.3% in the wood creosote group and 95.2% in the loperamide group) had abdominal cramping as the predominant associated symptom. The median (interquartile range [IQR]) TTLUS was similar between groups (24.4 [6.3-36.8] and 22.1 [3.5-32.1] hours in the wood creosote and loperamide groups, respectively), as was the median (IQR) time to total relief (31.0 [15.7-47.8] and 28.5 [13.5-43.5] hours in the wood creosote and loperamide groups, respectively). The mean (SD) numbers of unformed stools on day 1 were 3.31 (2.15) and 2.22 (1.25) in the wood creosote and loperamide groups, respectively (P < 0.002). The percentages of patients with improved or resolved abdominal cramping at the end of day 1 were 92.5% (49/53) and 78.0% (46/59) in the wood creosote and loperamide groups, respectively (P < 0.038). Both medications were well tolerated in the population studied.


CONCLUSIONS
Wood creosote and loperamide had comparable antidiarrheal effects in these patients with acute, nonspecific diarrhea. Wood creosote appeared somewhat more efficacious in improving or resolving abdominal cramping, whereas loperamide appeared somewhat more efficacious in improving diarrhea. Both treatments were well tolerated.
Kuge
Tomoo
T
Taiko Pharmaceutical Company, Ltd., 3-34-14 Uchihonmachi, Suita-City 564-0032, Osaka, Japan. kuge@seirogan.co.jp
Shibata
Takashi
T
Willett
Michael S
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000930:Antidiarrheals / Q000627:therapeutic use*; D003085:Colic / Q000188:drug therapy; D003407:Creosote / Q000627:therapeutic use*; D003967:Diarrhea / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008139:Loperamide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D000930:Antidiarrheals; D010936:Plant Extracts; C050412:seirogan; D008139:Loperamide; D003407:Creosote