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Pharmaceutics 2017, 9(3), 28; doi:10.3390/pharmaceutics9030028

Theophylline-7β-d-Ribofuranoside (Theonosine), a New Theophylline Metabolite Generated in Human and Animal Lung Tissue

1
Departments of Pharmacology and Therapeutics, Internal Medicine, and Pediatrics and Child Health, Max Rady College of Medicine, Centre on Aging, and College of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0T6, Canada
2
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada
*
Author to whom correspondence should be addressed.
Received: 29 June 2017 / Revised: 26 July 2017 / Accepted: 6 August 2017 / Published: 14 August 2017
(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)
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Abstract

While assessing the ability of mammalian lung tissue to metabolize theophylline, a new metabolite was isolated and characterized. The metabolite was produced by the microsomal fraction of lungs from several species, including rat, rabbit, dog, pig, sheep and human tissue. Metabolite production was blocked by boiling the microsomal tissue. This new metabolite, theophylline-7β-d-ribofuranoside (theonosine), was confirmed by several spectral methods and by comparison to an authentic synthetic compound. Tissue studies from rats, rabbits, dogs, and humans for cofactor involvement demonstrated an absolute requirement for NADP and enhanced metabolite production in the presence of magnesium ion. It remains to be demonstrated whether theonosine may contribute to the known pharmacological effects of theophylline. View Full-Text
Keywords: theophylline; theophylline metabolism; lung; microsomes; theophylline-7β-d-ribofuranoside; theonosine theophylline; theophylline metabolism; lung; microsomes; theophylline-7β-d-ribofuranoside; theonosine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sitar, D.S.; Bowen, J.M.; He, J.; Tesoro, A.; Spino, M. Theophylline-7β-d-Ribofuranoside (Theonosine), a New Theophylline Metabolite Generated in Human and Animal Lung Tissue. Pharmaceutics 2017, 9, 28.

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