Document Detail


Comparison of theophylline and theobromine metabolism in man.
MedLine Citation:
PMID:  2867879     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The total plasma and partial metabolic and renal clearances of theobromine and theophylline were determined in 13 healthy volunteers. Total plasma clearance for theobromine was 46% greater than that for theophylline, but the unbound clearances were almost identical. Theobromine renal clearance was 67% greater than that for theophylline but most of the difference was due to the lower protein binding of theobromine (free fraction = 0.86 compared to 0.58 for theophylline). Clearance by N-demethylation at the 3-position was 3.7-fold higher (unbound clearance 2.5-fold higher) for theobromine than for theophylline, showing that the position of the other methyl substituent (positions 1 or 7) is a major determinant of metabolic rate. There was a high degree of correlation between theophylline and theobromine plasma clearances (r = 0.86) and also between partial metabolic clearances both within drugs and across drugs (r = 0.65-0.99). The renal clearances of theophylline and theobromine were also correlated (r = 0.71). The results support the view that theophylline and theobromine are metabolized by a common group of cytochromes P-450 under similar regulatory control. Theobromine is a good model compound for assessing the activity of these enzymes in man as it has low pharmacological activity and low protein binding, its total and partial metabolic clearances correlate closely with those of theophylline, and close to 100% of the dose can be recovered as known metabolites.
Authors:
D J Birkett; R Dahlqvist; J O Miners; A Lelo; B Billing
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  13     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:    1985 Nov-Dec
Date Detail:
Created Date:  1986-03-07     Completed Date:  1986-03-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  725-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Dealkylation
Female
Humans
Male
Oxidation-Reduction
Theobromine / metabolism*,  urine
Theophylline / metabolism*,  urine
Chemical
Reg. No./Substance:
58-55-9/Theophylline; 83-67-0/Theobromine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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