Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arbaprostil [(15R)-15-methylprostaglandin E2] is an antiulcer prodrug being evaluated for the treatment of gastric and duodenal ulcers in humans. It epimerizes in acidic gastric fluid to produce the biologically active form, (15S)-15-methyl-PGE2, which acts directly on the gastric mucosa and possesses both gastric acid antisecretory and cytoprotective properties. Because of its local mode of action, plasma levels of the two epimers may have greater relevance to drug safety than to therapeutic efficacy. In the present study, plasma concentrations of both 15-methyl-PGE2 epimers resulting from a gastric acid antisecretory dose of arbaprostil oral solution (50 micrograms) were measured in eight male volunteers having sufficient gastric acidity for prodrug activation (pH less than 3). Arbaprostil was determined with a newly developed RIA having a sensitivity of 10 pg X mL-1. The accuracy of the RIA was confirmed by parallel analysis of plasma samples by HPLC. (15S)-15-Methyl-PGE2 was also determined by HPLC. Arbaprostil was both rapidly absorbed and eliminated (tmax of 15-30 min and plasma t1/2 of 20 min), but there was large intersubject variability in its observed maximum plasma concentration (38 to 348 pg X mL-1). The concentration of (15S)-15-methyl-PGE2 did not exceed 25 pg X mL-1 In six subjects and 50 pg X mL-1 in the remaining two subjects. The significance of these results is discussed.
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PMID:Plasma levels of the prodrug, arbaprostil, [(15R)-15-methylprostaglandin E2], and its active, antiulcer (15S) epimer in humans after single dose oral administration. 382 Jan 7

Arbaprostil [15(R),15-methyl prostaglandin E2] is inactive. In the presence of acid it is converted to the active 15(S) configuration. The degree of acidity needed for the conversion is not known. We inferred the degree of conversion in vivo in man at different gastric pHs by administering arbaprostil to normal volunteers whose gastric pH was maintained constant at various levels by intragastric titration. A pH-dependent inhibition of gastric acid secretion after stimulation with a peptone meal was observed, with 100 micrograms inhibiting 98% of acid production at pH 2, but only 15% at pH 6. Significant gastric acid inhibition occurred with the gastric pH at, or less than, 5.
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PMID:Gastric antisecretory activity of arbaprostil as affected by gastric pH. 400 43