Biodisposition of theophylline. I. Genetic variation in inbred mice

[8-14C]Theophylline was infused into mice with an osmotic minipump. Theophylline and its metabolites were separated from urine, blood, and feces by high-performance liquid chromatography and the radioactivity was determined by liquid-scintillation counting. The strains examined were SJL, DBA/2, C57BL/6, A/J, C3H/HeJ, AKR, SWR, and BALB/c. The theophylline clearance ranged from 479 +/- 30 ml/kg/hr in the A/J strain to 845 +/- 58 ml/kg/hr in the SJL strain. The total clearance in the A/J strain was signficantly different (p < 0.05) from that in the BALB/c, C57BL/6, and SJL strains. The metabolic pathway primarily responsible for this variation was the production of 1,3-dimethyluric acid.