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Relationship Between Vitamin B-6 Status and Elevated Pyridoxal Kinase Levels Induced by Theophylline Therapy in Humans¹

Department of Chemical Pathology, University of Pretoria, Pretoria 0001, South Africa

Theophylline administration to seven healthy male volunteers resulted in a rapid and significant decline in both plasma and erythrocyte pyridoxal-5'-phosphate levels. Total erythrocyte pyridoxal kinase levels increased during 15 wk of theophylline treatment from a mean initial activity of 19.23 ± 5.03 (mean ± SD) to 62.64 ± 11.59 nmol pyridoxal-5'-phosphate formed/(g hemoglobin·h). Although plasma pyridoxal levels remained normal, the threefold increase in total erythrocyte pyridoxal kinase activity levels did not normalize plasma and erythrocyte pyridoxal-5'-phosphate levels. Pyridoxal-5'-phosphate hydrolysis was not affected by theophylline therapy. Increased pyridoxal oxidation was confirmed by elevated urinary 4-pyridoxic acid excretion after 15 wk of theophylline treatment. Mean erythrocyte alanine aminotransferase activity declined by 70%, and aspartate aminotransferase activity declined by 50%, indicating that decreased availability of pyridoxal-5'-phosphate can have widespread metabolic consequences. We conclude that the effect of theophylline on vitamin B-6 metabolism is not transitory and cannot be overcome by elevated intracellular levels of pyridoxal kinase. However, pyridoxine supplementation (10 mg/d for 1 wk) normalized indices of vitamin B-6 status and reversed the downward trend in both alanine aminotransferase and aspartate aminotransferase activity levels.

KEY WORDS: • theophylline • vitamin B-6 • pyridoxal kinase • humans

¹ Financial support from Vesta Medicines (Pty.) Ltd. and the South African Medical Research Council is gratefully acknowledged.

² Institute for Biostatistics, South African Medical Research Council, Pretoria, South Africa.

Manuscript received 29 January 1990. Revision accepted 14 May 1990.