Intragastric acidity and omeprazole exposure during dosing with either PA32540 (enteric-coated aspirin 325 mg + immediate-release omeprazole 40 mg) or enteric-coated aspirin 325 mg + enteric-coated omeprazole 40 mg - a randomised, phase 1, crossover study.
Aliment Pharmacol Ther
; 38(1): 62-71, 2013 Jul.
Article
en En
| MEDLINE
| ID: mdl-23692061
BACKGROUND: Aspirin therapy is associated with adverse upper gastrointestinal effects. PA32540 is a coordinated-delivery tablet containing enteric-coated aspirin (EC-ASA) 325 mg and immediate-release (IR) omeprazole 40 mg. Immediate-release omeprazole (located in outer layer of tablet) is available for instantaneous dissolution rapidly after ingestion, while dissolution of the EC-ASA core is delayed until pH >5.5. AIM: To compare the pharmacodynamic and pharmacokinetic effects of PA32540 (EC-ASA 325 mg + IR-omeprazole 40 mg) vs. enteric-coated (EC)-omeprazole 40 mg. METHODS: This single-centre, open-label, randomised, two-way crossover study in healthy volunteers compared 7 days of once-daily dosing with PA32540 with 7 days of once-daily EC-ASA 325 mg + EC-omeprazole 40 mg dosed concomitantly. The primary endpoint was per cent time intragastric pH >4 over 24 h on Day 7. A key secondary endpoint was determination of the pharmacokinetics of omeprazole and salicylic acid. RESULTS: Twenty-six subjects (mean age 29 years) were enrolled into the study. On Day 7, mean per cent time intragastric pH >4 was 50.6% for PA32540 and 57.6% for EC-omeprazole 40 mg (P = 0.004) and geometric least squares mean AUC0-24 for omeprazole was 1446 h*ng/mL for PA32540 and 2558 h*ng/mL for EC-omeprazole 40 mg. Day 7 median Tmax of omeprazole was 0.5 h for PA32540 and 1.25 h for EC-omeprazole 40 mg. CONCLUSION: Total exposure to omeprazole from PA32540 was 57% of that from EC-omeprazole for the same dose amount (40 mg), while absolute difference in 24-h acid control was 7%. Omeprazole exposure and pH control with PA32540 appear similar to EC-omeprazole 20 mg.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Omeprazol
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Antiinflamatorios no Esteroideos
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Aspirina
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Ácido Gástrico
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Antiulcerosos
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Aliment Pharmacol Ther
Asunto de la revista:
FARMACOLOGIA
/
GASTROENTEROLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido