BACKGROUND:Omeprazole is a proton-pump inhibitor that acts to reduce acid secretion in the stomach and is used for treating various acid-related gastrointestinal disorders. There are several generic formulations of omeprazole available in Mexico; however, a literature search failed to identify published data concerning the bioavailability of these formulations in the Mexican population. OBJECTIVE: The aim of this study was to compare the bioavailability of 2 oral formulations of omeprazole 20-mg capsules, marketed for use in Mexico, in healthy volunteers: Inhibitron (test formulation) and LosecA 20 mg (reference formulation). METHODS: This study used a single-dose, open-label, randomized sequence, 2 x 2 crossover (2 administration periods x 2 treatments) design to compare the 2 formulations. Eligible subjects were healthy adult Mexican volunteers of both sexes. Subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test formulation followed by the reference formulation, or vice versa, with a 7-day washout period between administration periods. After a 12-hour (overnight) fast, subjects received a single, 20-mg dose of the corresponding formulation. Plasma samples were obtained over a 12-hour period after administration. Plasma omeprazole concentrations were analyzed by a nonstereospecific high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and 0.17, 0.33, 0.50, 0.75, 1, 1.25, 1.50, 1.75, 2, 2.50, 3, 4, 6, 8, and 12 hours after administration. The formulations were considered bioequivalent if the natural log (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125%, and if P <or= 0.05 for the 90% CIs. Tolerability was determined by clinical assessment, monitoring vital signs, laboratory analysis results, and subject interviews regarding adverse events (AEs). AEs were considered serious when the patient outcome was death, life threatening, required hospitalization, led to disability, or required intervention to prevent permanent impairment or damage. RESULTS:Thirty-four subjects were enrolled and completed the study (25 men and 9 women; mean [SD] age, 24.7 [5.5] years; weight, 64.3 [8.9] kg; and height, 167 [8] cm). Seventeen subjects received the test formulation first. No period or sequence effect was observed. The 90% CIs for the corresponding differences of ln C(max), ln AUC(0-t), and ln AUC(0-infinity) were 86.70% to 109.76%, 93.81% to 108.22%, and 102.09% to 114.21%, respectively (all, P<0.05), meeting the predetermined criteria for bioequivalence. Eight patients experienced 13 AEs that appeared to be not associated with study drug administration; none of the AEs were considered serious. CONCLUSIONS: In this small study in healthy Mexican adult volunteers, a single, 20-mg dose of the test formulation appeared to be bioequivalent to the reference formulation, based on the rate and extent of absorption. Both formulations were generally well tolerated.
RCT Entities:
BACKGROUND:Omeprazole is a proton-pump inhibitor that acts to reduce acid secretion in the stomach and is used for treating various acid-related gastrointestinal disorders. There are several generic formulations of omeprazole available in Mexico; however, a literature search failed to identify published data concerning the bioavailability of these formulations in the Mexican population. OBJECTIVE: The aim of this study was to compare the bioavailability of 2 oral formulations of omeprazole 20-mg capsules, marketed for use in Mexico, in healthy volunteers: Inhibitron (test formulation) and LosecA 20 mg (reference formulation). METHODS: This study used a single-dose, open-label, randomized sequence, 2 x 2 crossover (2 administration periods x 2 treatments) design to compare the 2 formulations. Eligible subjects were healthy adult Mexican volunteers of both sexes. Subjects were randomly assigned in a 1:1 ratio to receive a single 20-mg dose of the test formulation followed by the reference formulation, or vice versa, with a 7-day washout period between administration periods. After a 12-hour (overnight) fast, subjects received a single, 20-mg dose of the corresponding formulation. Plasma samples were obtained over a 12-hour period after administration. Plasma omeprazole concentrations were analyzed by a nonstereospecific high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to time t (AUC(0-t)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were drawn at baseline and 0.17, 0.33, 0.50, 0.75, 1, 1.25, 1.50, 1.75, 2, 2.50, 3, 4, 6, 8, and 12 hours after administration. The formulations were considered bioequivalent if the natural log (ln)-transformed ratios of C(max) and AUC were within the predetermined equivalence range of 80% to 125%, and if P <or= 0.05 for the 90% CIs. Tolerability was determined by clinical assessment, monitoring vital signs, laboratory analysis results, and subject interviews regarding adverse events (AEs). AEs were considered serious when the patient outcome was death, life threatening, required hospitalization, led to disability, or required intervention to prevent permanent impairment or damage. RESULTS: Thirty-four subjects were enrolled and completed the study (25 men and 9 women; mean [SD] age, 24.7 [5.5] years; weight, 64.3 [8.9] kg; and height, 167 [8] cm). Seventeen subjects received the test formulation first. No period or sequence effect was observed. The 90% CIs for the corresponding differences of ln C(max), ln AUC(0-t), and ln AUC(0-infinity) were 86.70% to 109.76%, 93.81% to 108.22%, and 102.09% to 114.21%, respectively (all, P<0.05), meeting the predetermined criteria for bioequivalence. Eight patients experienced 13 AEs that appeared to be not associated with study drug administration; none of the AEs were considered serious. CONCLUSIONS: In this small study in healthy Mexican adult volunteers, a single, 20-mg dose of the test formulation appeared to be bioequivalent to the reference formulation, based on the rate and extent of absorption. Both formulations were generally well tolerated.