Depression of vitamin B6 levels due to theophylline

Theophylline overdosage can cause life-threatening symptoms, that include seizures and cardiac arrhythmias, and can be fatal. Neither the onset of toxicity nor the severity of symptoms is well predicted by serum theophylline concentrations. Since depressed vitamin B6 plasma levels can occur in patients receiving theophylline, we explored a B6-theophylline interaction in a rabbit model. Administration of theophylline preparations intraperitoneally (aminophylline) or orally (sustained release anhydrous theophylline) resulted in a 47% depression of plasma pyridoxal 5'-phosphate (PLP) levels. The 87% increase in PLP with pyridoxine administration was only 18% when aminophylline was also given. The mechanism of the theophylline-B6 interaction is obscure. Ethylenediamine in some theophylline preparations binds directly to PLP, potentially increasing the less direct theophylline effect. Pyridoxine supplementation resulted in higher average PLP levels but did not prevent death in animals with profoundly low PLP levels. If these data apply to humans, B6 deficiency may contribute to chronic theophylline toxicity; however, pyridoxine administration in the dosage used may not prevent toxicity. Larger doses may prove beneficial after further investigation.