Pharmacotherapeutic Group: Gastritis and gastric ulcer treatment.
Pharmacology: Terpenes are naturally-occurring organic substances that are found in essential oils and in tree and plant resins. They have long been known for their ability to aid in tissue repair.
Teprenone, the active ingredient of SELBEX, is a terpene analogue. It accelerates the biosynthesis of high molecular weight glycoproteins and phospholipids - major components of gastric mucosa and mucus that are involved in the regeneration and defense of gastric mucosa. Teprenone also increases bicarbonate concentrations in gastric mucus. In addition, it prevents or reverses reductions in proliferative capacity of mucosal cells that can be caused by gastric mucosal lesions and promotes repairing of mucosal lesions.
Teprenone has been found to have excellent clinical efficacy in the treatment of acute gastritis, acute exacerbation of chronic gastritis and gastric ulcers.
Anti-ulcer effect: Teprenone has been demonstrated to show a potent anti-ulcer effect against various experimental ulcers in rats (caused by cold-restraint, indomethacin, aspirin, prednisolone, reserpine, acetic acid, thermocautery or aspirin-cold-restraint) and to be very effective against various experimental gastric mucosal lesions (caused by hydrochloric acid, aspirin, ethanol, or radiation).
Further, in an experiment using rats, teprenone has been demonstrated to inhibit gastric mucosal lesions due to compound 48/80 or platelet activating factor (PAF) in which active oxygen is thought to be involved.
Increase of gastric mucus: Teprenone promotes mucus synthesis and secretion in cultured gastric mucosal epithelial cells of rat origin.
When present in the superficial mucous cells and neck cells, teprenone increases the output of mucus from these cells in rats.
Teprenone increases activities of synthetases mediating the biosynthesis of high-molecular glycoprotein in rats and phospholipids in guinea pigs, the main factors for gastric mucosal regeneration and protection, and promotes the synthesis and secretion of high-molecular glycoprotein and phospholipids in rats and humans.
In addition, it has also been demonstrated in rats and rabbits that teprenone increases the bicarbonate content of the gastric mucus.
Cytoprotect effect due to induction of heat shock proteins (HSP) genesis: Teprenone induces genesis of HSP60, 70, 90 in gastric mucosal cells and shows cytoprotect effect in guinea pigs.
Increase of gastric mucosal prostaglandins: Teprenone increases the content of prostaglandin E
2 and I
2 in the gastric mucus of rats. In rats, the mechanism for this has been demonstrated to be an increase in prostaglandin synthetase activity.
Increase and improvement of gastric mucosal blood flow: Teprenone increases gastric mucosal blood flow in humans. Teprenone rectifies the decrease in gastric mucosal blood flow in water-immersion restrained rats.
Protection of the gastric mucosa: Teprenone inhibits ethanol-induced injury of the gastric mucosa in rats.
Teprenone inhibits ethanol-induced injury of the gastric mucosa in healthy adult male volunteers.
Maintenance of the homeostasis of the gastric mucosal cell proliferation zone: Teprenone enhances gastric mucosal cell proliferation which has been reduced by hydrocortisone in mice, thus helping to maintain the homeostasis of the gastric mucosal cell proliferation zone. Teprenone promotes gastric mucosal regeneration and injured gastric mucosal repair in acetic acid ulcers in rats.
Inhibition of lipid peroxidation: Teprenone inhibits both gastric mucosal injury due to burning as well as increases in lipid peroxide levels in the gastric mucosa in rats.
Clinical Studies: Clinical Efficacy: SELBEX was useful for treatment of acute gastritis and acute exacerbation stage of chronic gastritis in a double-blind clinical trial. The General Improvement Rating (GIR) of SELBEX for patients with gastritis was "markedly improved" in 48% (12/25) and "moderately improved" or better in 92% (23/25).
GIR was determined from the improvement rating for endoscopic findings and the improvement rating for subjective or objective symptoms.
SELBEX was useful for treatment of peptic ulcers in a double-blind clinical trial. The Final Global Improving Ratio (FGIR) of SELBEX for patients with gastric ulcers was "markedly improved" in 47% (61/131) and "slightly improved" or better in 93% (122/131).
FGIR was evaluated by coordinating the findings of endoscopy and roentgenography with the degree of improvement of subjective and objective symptoms.
Pharmacokinetics: Blood concentration: Three capsules of SELBEX Capsules or 1.5 g of SELBEX Fine Granules 10% (150 mg of teprenone) were administered orally to twelve healthy adult male volunteers after a meal in a cross-over design. The serum teprenone concentrations were determined and are shown in the following figure (see Figure 1). The maximum drug concentrations (C
max) and the area under the plasma concentration curve (AUC
0-32) are shown in the following table (see Table 2). There was no significant difference in C
max or AUC
0-32 between the 2 dosage forms. (See Figure 1 and Table 1.)
Click on icon to see table/diagram/image
Click on icon to see table/diagram/image
Effect of meal: Three capsules of SELBEX Capsules (150 mg of teprenone) were administered orally to eighteen healthy adult male volunteers at 30 min. 1 hr or 3 hr after a meal in a cross-over design. The plasma teprenone concentrations were determined and are shown in the following figure and table (see Figure 2 and Table 2). The area under the plasma concentration-time curve (AUC) at 30 min after a meal is comparable with that at 1 hr after a meal. The AUC at 3 hr after a meal was 23% lower than that at 30 min after a meal. (See Figure 2 and Table 2.)
Click on icon to see table/diagram/image
Click on icon to see table/diagram/image