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RESEARCH PRODUCT

Variability in individual response to various doses of omeprazole. Implications for antiulcer therapy.

subject

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This study was carried out in order to perform a combined prospective assessment of the individual pharmacodynamic response and of duodenal ulcer healing in patients treated with three different doses of omeprazole. Ninety-nine patients with endoscopically proven duodenal ulcers were subdivided into three parallel groups of 33 cases, who were randomly assigned to receive orally at 0800 hr, in single blind fashion, either 10 mg, 20 mg, or 40 mg of omeprazole. All of them underwent continuous intragastric pH monitoring both in basal conditions and on the fifth day of each dose regimen; ulcer healing was then assessed endoscopically after four weeks of treatment. All three doses of omeprazole caused pH values to increase significantly (P<0.001) over the whole 24-hr period. In patients treated with omeprazole 10 mg, the individual responses showed the highest variability: the acid inhibition, expressed in terms of time spent above pH 3.0, lasted for more than 16 hr in 42% of cases, for more than 8 hr in 28%, and for less than 6 hr in 30%. In patients treated with omeprazole 20 mg, the pharmacological response was more marked and uniform and lasted for more than 16 hr in 79% of cases; however, it is worth noting it lasted for less than 6 hr in three patients (10%). In patients treated with omeprazole 40 mg, the individual response was excellent (more than 16 hr) in 94% of cases, and it lasted for less than 6 hr in only one patient (3%). The mean durations of antisecretory effect of 10, 20 and 40 mg of omeprazole were 13.21, 19.10, and 21.45 hr, and the respective four-week healing rates were 68%, 87%, and 98%. Thus, the longer-lasting the acid inhibition, the higher the healing rate (P<0.05). A dose of omeprazole as low as 10 mg produces a consistent acid inhibition in 70% of cases, and this can be associated with frequent, but unpredictable, clinical benefit. The acid suppression obtained with omeprazole 20 mg is remarkable in the majority of patients, but is poor in 10% of cases, and this finding may result in clinical nonresponse. The 40-mg dose of omeprazole produces the most uniform response and is only occasionally unsuccessful in the clinical setting.