Drug-pyridoxal phosphate interactions.

In this review it has been pointed out that vitamin B6 and its vitamers can be involved in many interactions with a number of drugs, as well as with the actions of various endocrines and neurotransmitters. Nutritional deficiencies, especially of vitamins and proteins, can affect the manner in which drugs undergo biotransformation, and thereby may also modify the therapeutic efficacy of certain drugs. The differences between nutritional vitamin B6 deficiency and the hereditary disorder producing pyridoxine dependency are discussed. In addition to a pyridoxine deficiency being able to adversely affect drug actions, the improper supplementation with vitamin B6 can in some instances also adversely affect drug efficacy. A decrease by pyridoxine in the efficacy of levodopa used in the treatment of Parkinsonism is an example. The interrelationships and enzymatic interconversions among pyridoxine vitamers, both phosphorylated and non-phosphorylated, are briefly discussed, particularly regarding their pharmacokinetic properties. The ways in which the normal biochemical functions of vitamin B6 may be interfered with by various drugs are reviewed. (1) The chronic administration of isoniazid for the prevention or treatment of tuberculosis can produce peripheral neuropathy which can be prevented by the concurrent administration of pyridoxine. An acute toxic overdose of isoniazid causes generalized convulsions, and the intravenous administration of pyridoxine hydrochloride will prevent or stop these seizures. (2) The acute ingestion of excessive monosodium glutamate will, in some individuals, cause a group of symptoms including among others headache, weakness, stiffness, and heartburn, collectively known as the 'Chinese Restaurant Syndrome.' These symptoms can be prevented by prior supplementation with vitamin B6. The beneficial effect is ascribed to the correction of a deficiency in the activity of glutamic oxaloacetic transaminase, an enzyme that is dependent on pyridoxal phosphate. Some interesting relationships are pointed out between vitamin B6, picolinic acid, and zinc. It is postulated that the intestinal absorption of zinc is facilitated by picolinic acid, a metabolite of tryptophan. The derivation of picolinic acid from tryptophan depends on the action of the enzyme kynureninase, which is dependent on pyridoxal phosphate; therefore, the adequate absorption of zinc is indirectly dependent on an adequate supply of vitamin B6. The formation of pyridoxal phosphate, on the other hand, appears to be indirectly dependent on Zn2++ which activates pyridoxal kinase.(ABSTRACT TRUNCATED AT 400 WORDS)