Theophylline disposition during acute and chronic hypoxia in the conscious dog

It has been reported in experimental models that acute hypoxia reduced the activity of the hepatic cytochrome P-450. The objective of the present study was to investigate in conscious dogs whether acute and chronic hypoxia will influence the disposition of theophylline. To this purpose 6 beagle dogs received 8 mg/kg i.v. of theophylline while breathing air, after acute hypoxia (PaO2 of 48.5 +/- 0.3 mmHg) and after 96 hours of hypoxia. Theophylline and metabolites, 3-methylxanthine and 1,3-dimethyluric acid, were assayed by HPLC. Theophylline volume of distribution, while breathing air, was 0.51 +/- 0.03 L/kg and was not affected by hypoxia. Theophylline metabolic and renal clearances were 1.53 +/- 0.24 and 0.18 +/- 0.04 mL/min/kg and remained constant when the dogs were hypoxic. The urinary recovery of theophylline and metabolites was not affected by acute or chronic hypoxia. It is concluded, that in the dog hypoxia does not affect the disposition of theophylline.