title: Evidence of a theophylline-induced vitamin B6 deficiency caused by noncompetitive inhibition of pyridoxal kinase.
abstract: 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 2.7.1.35) 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 1.4.3.5) 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.
authors.affiliation: Department of Chemical Pathology, University of Pretoria, South Africa.
authors.forename: J B
authors.initials: JB
authors.lastname: Ubbink
authors.forename: R
authors.initials: R
authors.lastname: Delport
authors.forename: P J
authors.initials: PJ
authors.lastname: Becker
authors.forename: S
authors.initials: S
authors.lastname: Bissbort
mesh_terms: D000328:Adult; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D008297:Male; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011731:Pyridoxal Kinase / Q000037:antagonists & inhibitors*; D011732:Pyridoxal Phosphate / Q000097:blood; D013806:Theophylline / Q000009:adverse effects* / Q000097:blood; D026681:Vitamin B 6 Deficiency / Q000139:chemically induced*
chemical_list: D011732:Pyridoxal Phosphate; D013806:Theophylline; D010770:Phosphotransferases; D011731:Pyridoxal Kinase