Evidence of a theophylline-induced vitamin B6 deficiency caused by noncompetitive inhibition of pyridoxal kinase

J Lab Clin Med. 1989 Jan;113(1):15-22.


A placebo-controlled, double-blind study indicated that theophylline administration to apparently healthy, young men induced significantly depressed plasma pyridoxal-5'-phosphate levels. Plasma pyridoxal levels were not affected by theophylline therapy. The effect of theophylline on circulating pyridoxal-5'-phosphate levels is explained by the observation that theophylline acts as a noncompetitive inhibitor for erythrocyte pyridoxal kinase (EC with an apparent inhibition constant (Ki) of 1.28 x 10(-5) mol/L. Theophylline did not affect erythrocyte pyridoxamine (pyridoxine)-5'-phosphate oxidase (EC activity. During theophylline therapy, erythrocyte pyridoxal kinase levels increased nearly twofold from an initial mean level of 24.2 +/- 4.0 (+/- SD) nmol to 46.9 +/- 7.3 nmol pyridoxal-5'-phosphate per gram of hemoglobin per hour. This partially counteracted the effect of theophylline on vitamin B6 metabolism. Nevertheless, erythrocyte pyridoxal-5'-phosphate levels in subjects given theophylline decreased significantly (p = 0.03) from pretreatment levels. The oral tryptophan load test resulted in significantly (p = 0.007) increased urinary xanthurenic acid excretion after 4 weeks of theophylline therapy. Both plasma pyridoxal-5'-phosphate levels and the tryptophan load test results normalized after 1 week of pyridoxine supplementation, indicating that 10 mg pyridoxine per day was effective to counteract the antagonistic effect of short-term theophylline therapy on vitamin B6 metabolism.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Erythrocytes / metabolism
  • Humans
  • Male
  • Phosphotransferases / antagonists & inhibitors*
  • Pyridoxal Kinase / antagonists & inhibitors*
  • Pyridoxal Phosphate / blood
  • Theophylline / adverse effects*
  • Theophylline / blood
  • Vitamin B 6 Deficiency / chemically induced*


  • Pyridoxal Phosphate
  • Theophylline
  • Phosphotransferases
  • Pyridoxal Kinase