Effect of single and repeated intravenous doses of omeprazole on pentagastrin stimulated gastric acid secretion and pharmacokinetics in man

Abstract

Single intravenous doses of 10, 20, 40, and 80 mg and repeated once daily intravenous doses of 10 and 20 mg omeprazole induced a powerful and long lasting inhibition of pentagastrin stimulated gastric acid secretion (PAO) in healthy male volunteers. Single intravenous doses of 10, 20, 40 and 80 mg omeprazole inhibited PAO by 30% (p < 0.01), 45% (p < 0.01), 61% (p < 0.01), and 80% (p < 0.01), respectively when measured 1.5 h after dose, and by 20% (NS), 27% (NS), 36% (p < 0.01) and 59% (p < 0.01), respectively when measured 24 h after dose. Six days after repeated once daily intravenous doses of 10 and 20 mg omeprazole, PAO was inhibited by 63% (p < 0.01) and 82% (p < 0.01), respectively when measured 1.5 h after dose, and by 32% (p < 0.01) and 43% (p < 0.01), respectively when measured 24 h after dose. The inhibition of PAO by 10 mg administered intravenously as a single bolus injection was comparable with the inhibition by 20 mg as a single oral dose. Repeated once daily administration of 10 mg intravenously and 20 mg orally also resulted in comparable reductions in PAO. The reduction in PAO after repeated once daily oral administration of 20 mg was comparable with the effects of a single intravenous dose of 40 mg. Terminal half lives were short, but significantly (p < 0.05) prolonged after a single intravenous injection of 80 mg. Repeated once daily intravenous administration of 10 and 20 mg did not result in prolongation of terminal half lives. It is concluded that intravenous administration of omeprazole causes a potent and long acting inhibition of pentagastrin stimulated gastric acid secretion in man. Its potency is augmented after repeated once daily administration.