Plasma Levels of the Prodrug, Arbaprostil, [(15R)-15-Methylprostaglandin E2], and its Active, Antiulcer (15S) Epimer in Humans after Single Dose Oral Administration

Cox, James H.; Bothwell, W; Pullen, Robert H.; Wynalda, Michael A.; Fitzpatrick, Francis A.; VanderLugt, James T.

doi:10.1002/jps.2600751118

Cited by 9 publications

(1 citation statement)

References 17 publications

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“…While the chemical structure of the unknown compound cannot be conclusively related to limonin on the basis of the information available, its appearance in the plasma of the human subjects confirms that another compound with the same molecular weight as limonin is produced in humans administered high doses of limonin glucoside. Previous reports of epimerization of chiral centers of steroidal (25), prostaglandin (26), imidazole (27), and alkaloid (28) drug metabolites in humans illustrates epimerization in human metabolism and supports the theory that the epimerization of limonin to epilimonin may proceed in the metabolism of limonin glucoside by humans.…”

Section: Discussionsupporting

confidence: 62%

Bioavailability of Citrus Limonoids in Humans

Manners

Jacob

Breksa

et al. 2003

J. Agric. Food Chem.

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This study utilizes liquid chromatography/mass spectrometry (LC-MS) to analyze the plasma of four groups of four healthy male and female subjects administered high doses of pure limonin glucoside (0.25-2.0 g in 200 mL of buffered water) for the presence of limonin to establish the absorption, metabolism, and bioavailability of citrus limonoids to humans. The plasma analysis revealed increasing amounts of limonin associated with increasing doses of limonin glucoside among the subject groups in mean maximum concentration amounts ranging from 1.74 to 5.27 nmol/L. A high degree of variability in the analyzed limonin concentration was observed within the subject groups. The mean time to maximum concentration was 6 h. A second compound with MS/MS characteristics identical to limonin was detected in amounts up to 5.13 nmol/L and is hypothesized to be a limonin epimer. Poststudy health evaluation established no ill effects among study subjects consuming high doses of limonin glucoside.

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Section: Discussionsupporting

confidence: 62%

Bioavailability of Citrus Limonoids in Humans

Manners

Jacob

Breksa

et al. 2003

J. Agric. Food Chem.

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Pharmacokinetic interactions between arbaprostil and aspirin in humans

Hsyu

Cox

Pullen

et al. 1989

Biopharm & Drug Disp

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Arbaprostil is an orally active prostaglandin E2 analogue. It has been developed as a drug to treat ulcers induced by non-steroidal anti-inflammatory drugs. In this study, pharmacokinetic interactions between arbaprostil and aspirin were examined in humans after chronic doses of both drugs. Subjects received either arbaprostil (50 micrograms), aspirin (975 mg) or arbaprostil (50 micrograms) and aspirin (975 mg) four times a day for 6 days and one dose on 7th day. Blood and urine samples were collected after the last dose for 6 h. Pharmacokinetic parameters of arbaprostil, aspirin, and salicylate were determined. Coadministration of arbaprostil significantly lowered the area under curve (5.09 +/- 0.32 micrograms hml-1 vs 5.78 +/- 0.29 micrograms hml-1, mean +/- SE, p less than 0.05) and time (0.45 +/- 0.07 h vs 0.70 +/- 0.12 h, p less than 0.05) to reach maximal plasma concentration of aspirin (acetylsalicylate). The pharmacokinetics of salicylate were not changed by arbaprostil, nor were the pharmacokinetics of arbaprostil affected by aspirin. Coadministration of these two drugs did not appear to potentiate the side-effects of either drug. The results suggest that arbaprostil and aspirin may be administered together without clinically significant changes in pharmacokinetics or adverse side-effects.

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The Contribution of Enantiomers to Variability in Response to Anti-Inflammatory Drugs

Day²

1988

Basis for Variability of Response to Anti-Rheumatic Drugs

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Plasma Levels of the Prodrug, Arbaprostil, [(15R)-15-Methylprostaglandin E2], and its Active, Antiulcer (15S) Epimer in Humans after Single Dose Oral Administration

Cited by 9 publications

References 17 publications

Bioavailability of Citrus Limonoids in Humans

Bioavailability of Citrus Limonoids in Humans

Pharmacokinetic interactions between arbaprostil and aspirin in humans

The Contribution of Enantiomers to Variability in Response to Anti-Inflammatory Drugs

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