PT  - JOURNAL ARTICLE
AU  - O Agostini
AU  - G Bonacchi
AU  - G Coppini
AU  - E Toja
AU  - A Triolo
AU  - S Manzini
AU  - G Pieraccini
AU  - G Moneti
TI  - Metabolism of isbufylline in humans. Isolation, identification, and synthesis of plasma and urine metabolites.
DP  - 1994 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 259--268
VI  - 22
IP  - 2
4099  - http://dmd.aspetjournals.org/content/22/2/259.short
4100  - http://dmd.aspetjournals.org/content/22/2/259.full
SO  - Drug Metab Dispos1994 Mar 01; 22
AB  - Isbufylline metabolism after oral administration to humans was studied. The main metabolites detected by the HPLC method, in plasma, were 1-methyl-7-(2-hydroxy-2-methyl-propyl) xanthine (I), 1,3-dimethyl-7-(2-hydroxy-2-methyl-propyl) xanthine (II), and 1-methyl-7-(2-methyl-propyl) xanthine (III). The main metabolites detected in urine were 1-methyl-7-(2-hydroxy-2-methyl-propyl) xanthine (I), 1,3-dimethyl-7-(2-carboxy-propyl) xanthine (IV), and 1,3-dimethyl-7-(2-hydroxymethyl-propyl) xanthine glucuronic acid (V)-Gluc. They were isolated by HPLC, identified by GC/MS, HPLC/MS, or HPLC/MS/MS, and finally synthesized. Recovery of these metabolites, along with the absence of unmetabolized isbufylline in the urine, indicated biotransformation and renal excretion as the main routes of isbufylline elimination in humans. HPLC quantitation of the characterized urine metabolites revealed that 49% of the drug was eliminated as (I), 9% as (V)-Gluc, and 5% as (IV).