Individual and group dose‐responses to intravenous omeprazole in the first 24 h: pH‐feedback‐controlled and fixed‐dose infusions.

Abstract

1. Individual responses to intravenous boli of omeprazole have shown considerable variability. Data on the individual responses to the new omeprazole infusion formulation are lacking. 2. Individual dose-responses in the first 24 h of fixed-dose and pH-feedback-controlled infusions of omeprazole were assessed in two randomised, third-party blinded, cross-over studies, using two separate groups of eight healthy subjects. In study A, feedback-controlled infusions of omeprazole (target pH 5, dose range 0-12 mg h-1) and fixed-dose infusions (8 mg h-1) were compared, both with an initial bolus of 80 mg. Omeprazole plasma concentrations were measured. Study B assessed the effect on individual pH-control of a loading bolus of either 40 mg or 80 mg omeprazole, followed by feedback-controlled infusions. 3. Study A: the median % time of pH > 5 was 71.2 (total range: 48.9-83.2) with feedback infusions and 57.9 (28.0-95.3) with fixed-dose infusions (P = 0.06). The mean 24 h infusion doses were 173.1 mg (44.5-253.1) in the feedback group and 192 mg in the fixed-dose group. The AUC of omeprazole plasma concentrations ranged widely, but correlated with the % time of pH > 5 during fixed-dose infusions. Study B: initial boli of 40 mg and 80 mg of omeprazole resulted in similar 24 h median % of time with pH > 5, 69.2 (49.9-78.8) and 69.6 (44.4-87.7), respectively. Mean omeprazole doses infused by feedback pump were 187.6 mg (83.1-253.6) after 40 mg boli and 159.9 mg (61.8-227.0) after 80 mg boli.(ABSTRACT TRUNCATED AT 250 WORDS)