Identification of two main urinary metabolites of (/sup 14/C)omeprazole in humans

Journal Article · Sun Jan 01 00:00:00 EST 1989 · Drug Metab. Dispos.; (United States)

OSTI ID:5767926

Renberg, L; Simonsson, R; Hoffmann, K J

The excretion and metabolism of (/sup 14/C)omeprazole given orally as a suspension was studied in 10 healthy male subjects. An average of 79% of the dose was recovered in the urine in 96 hr, with most of the radioactivity (76% of dose) being eliminated in the first 24 hr. Pooled urine (0-2 hr) from five subjects, containing about 47% of the dose, was analyzed by reverse phase gradient elution LC with radioisotope detection. Omeprazole was completely metabolized to at least six metabolites. The two major metabolites were extensively purified by LC and their structures were determined by MS with derivatization and use of stable isotopes, 1H NMR, and comparison with synthetic references. They were formed by hydroxylation of a methyl group in the pyridine ring, followed by further oxidation of the alcohol to the corresponding carboxylic acid. Both metabolites retained the sulfoxide group of omeprazole, rendering them as unstable as the parent compound at pH less than 7. They accounted for approximately 28% (hydroxyomeprazole) and 23% (omeprazole acid) of the amount excreted in the 0-2-hr collection interval. Based on in vitro studies with the synthetic metabolites in isolated gastric glands, it is unlikely that M1 and M2 will contribute to the pharmacological effect of omeprazole in humans.

• Research Organization: Department of Pharmacokinetics and Drug Metabolism, AB Haessle, Moelndal (Sweden)
• OSTI ID: 5767926
• Journal Information: Drug Metab. Dispos.; (United States), Vol. 17:1
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
DRUGS
METABOLISM
CARBON 14 COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAN
MASS SPECTROSCOPY
METABOLITES
NUCLEAR MAGNETIC RESONANCE
TRACER TECHNIQUES
ANIMALS
CHROMATOGRAPHY
ISOTOPE APPLICATIONS
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SPECTROSCOPY
VERTEBRATES
550501* - Metabolism- Tracer Techniques