Treatment of gastric ulceration with carbenoxolone sodium: clinical and radiological evaluation.

Abstract

Gastric ulcers have a natural tendency towards healing, and a controlled therapeutic trial is the only reliable method for assessing the value of any method of treatment. This paper reports our experience with carbenoxolone, and confirms the studies of Doll et al. (1962 (1958) showed that stopping smoking helped to heal gastric ulcers.In the trial of carbenoxolone reported by Doll et al. (1962), of 30 patients receiving the drug 70% healed by two-thirds or more, while of 20 patients receiving dummy tablets 20% healed by two-thirds or more. The figure for complete healing in their trial was 37%.Revers (1946) undertook the first clinical trial of an extract of liquorice in the treatment of gastric ulceration. He demonstrated a beneficial effect, but a large number of patients developed oedema and interest waned. Liquorice extracts contain glycyrrhizic acid ; from this may be prepared the triterpenoid glycyrrhetinic acid. The latter acid has a low solubility in body fluids, and a water-soluble derivative has been synthesized-that is, the disodium salt of glycyrrhetinic acid hydrogen succinate (carbenoxolone sodium). It differs from preparations containing liquorice extracts, where the action cannot be attributed to any one constituent. MethodAll in-patients and out-patients attending the medical clinics of the hospital in whom a gastric ulcer was demonstrated radiologically were admitted to the trial, provided there were no contraindications. A double-blind trial was adopted; the clinician and radiologist, as well as the patient, were unaware of the precise medication being administered for the first two weeks and sometimes four weeks of treatment.Forty sets of tablets were prepared, only 35 of which were used. Half of the tablets contained 50 mg. of carbenoxolone, together with starch B.P., lactose B.P., and peppermint oil. The remaining, or " dummy," tablets were identical in appearance. The sets of tablets were intermingled and each set was given a trial number. The key to the trial tablets was kept in a sealed envelope, which was not opened until the trial was completed. When patients were admitted to the trial they were given the trial tablets by the dispensary in numerical order. In this way a random allocation of patients to the active-tablet and dummy-tablet groups was obtained. * Carbenoxolone sodium is available under the branded name of Biogastrone and is abbreviated to carbenoxolone throughout this paper.

The Effects of Carbenoxolone on Human Myocardial Conduction

“…Repeat testing after carbenoxolone. Carbenoxolone (Biorex, London, United Kingdom) has been used as a treatment for peptic and oral ulceration since the 1960s at a dose of 100 to 200 mg/day (21). Carbenoxolone is absorbed rapidly and unchanged from the stomach, reaching 90% of their peak (15 g/ml) within 40 min of oral administration (22).…”

Medical Management of Peptic Ulcer With reference to anti-ulcer agents in other gastro-intestinal diseases

“…Minor side-effects of carbenoxolone: Occasional minor side-effects include headache and heartburn (Doll et al, 1962 ;Turpie and Thomson , 1965 ;Montgomery, 1967;Horwich and Galloway, 1965). In the series of Bank and Marks (1970) I patient developed galactorrhoea , 1 a bitter taste and a third a superficial venous thrombosis.…”

“…One problem relates to the extent to which they can occur as isolated phenomena. The most common complications are :-Hypertension , Fluid Retention and Hypokalaernia These effects have, to varying degrees, been found in up to 30 %of patients given 100 mg carbenoxolone sodium 3 times daily (Doll et al, 1962(Doll et al, , 1965(Doll et al, , 1968aHorwich and Galloway, 1965;Turpie and Thomson, 1965;Bank et al, 1967a;Montgomery , 1967;Rosch and Ottenjann, 1971) to 16 % of patients given 50 mg 3 times daily (Cocking and MacCaig, 1969). The rise in blood pressure may be substantial and may be in excess of 50 mm Hg systolic (Doll et al, 1968a, b).…”

“…Cushing's syndrome: Horwich and Galloway (1965) found a patient who developed a Cushingoid appearance while receiving carbenoxolone (without change in blood pressure, glucose tolerance or steroid secretion) which subsided when treatment was stopped.…”

Morphological observations on gastric ulcers treated with carbenoxolone sodium.

“…Carbenoxolone, being a pentacyclic triterpene, is a drug which has a steroid-like structure, and despite anitiinflammatory and mineralocorticoid-like effects resembling those of steroid has shown considerable success in producing healing of gastric ulceration (Doll, Hill, Hutton, and Underwood, 1962;Horwich and Galloway, 1965). The mode of action of carbenoxolone is not yet understood.…”