Theophylline increases pyridoxal kinase activity independently from vitamin B6 nutritional status.
Asthmatics treated with theophylline, a potent inhibitor of pyridoxal kinase and therefore a vitamin B6 antagonist, demonstrated a significant correlation (r = 0.71; p < 0.001) between drug plasma levels and erythrocyte pyridoxal kinase activities. A cross-over, placebo controlled study was completed on 15 healthy volunteers to investigate the mechanism by which theophylline induces pyridoxal kinase activity. The subjects were supplemented with vitamin B6 or placebo for two weeks before theophylline therapy was started. Vitamin B6 supplementation resulted in a four-fold increase in circulating pyridoxal 5'-phosphate levels, while placebo had no effect. When theophylline therapy was commenced, erythrocyte pyridoxal kinase activities increased significantly (p < 0.001) irrespective of whether vitamin B6 or placebo was supplemented. It is concluded that a depressed vitamin B6 status is not responsible for higher erythrocyte pyridoxal kinase activities encountered during theophylline therapy, but that the drug is directly responsible for elevated enzyme levels.
Delport
R
R
Department of Chemical Pathology, University of Pretoria, South Africa.
Ubbink
J B
JB
Vermaak
W J
WJ
Becker
P J
PJ
D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D008875:Middle Aged; D009752:Nutritional Status; D011731:Pyridoxal Kinase / Q000097:blood* / Q000187:drug effects; D011732:Pyridoxal Phosphate / Q000097:blood; D011736:Pyridoxine / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013806:Theophylline / Q000097:blood / Q000494:pharmacology*
D011732:Pyridoxal Phosphate; D013806:Theophylline; D011731:Pyridoxal Kinase; D011736:Pyridoxine