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)

Pyridoxine which is converted to pyridoxal 5-phosphate (vitamin B6), a cofactor for enzymatic decarboxylation and transamination of aromatic L-amino acids, may accelerate metabolism of L-dopa. To test this possibility, we studied the effect of pyridoxine administration on urinary excretion of DOPA and certain DOPA metabolittes following administration of L-DOPA to normal and Parkinsonian subjects.

The clinical state achieved with levodopa was compared to that on levodopa plus alpha-methyldopa hydrazine, which blocks conversion of levodopa to dopamine within peripheral tissues only. Five children with dystonia remained unimproved by either regimen. In 26 adults with Parkinsonism less levodopa was needed for symptomatic control when levodopa was given with inhibitor than when used alone. The amount of inhibitor that had to be added to similar doses of levodopa was less in patients who had received levodopa chronically. Rapid induction of therapy, better diurnal symptomatic control and a new capability to administer pyridoxine to patients receiving levodopa constituted advantages of adding inhibitor to levodopa. The main disadvantage of these combinations was the rapid induction of involuntary movements.

Exogenous pyridoxine is known to antagonize the neuropharmacologic action of levodopa in Parkinson disease. The metabolic interactions of levodopa, pyridoxine and carbidopa, a peripheral decarboxylase inhibitor, were studied in 15 long-term, levodopa-treated patients. Pyridoxine reduced plasma dopa levels 67% but enhanced homovanillic acid synthesis 49%. Carbidopa potentiated plasma dopa, inhibited homovanillic acid synthesis, and minimized the effects of pyridoxine. The decarboxylase activity index following pyridoxine administration increased 483% and 136% for plasma and urine respectively. Carbidopa effected a 77% and 94% reduction. It is suggested that pyridoxine accelerates systemic metabolism of levodopa, thereby decreasing availability of the amino acid to brain parenchyma. The combination of levodopa and carbidopa prevents the loss of levodopa effect produced by exogenous pyridoxine.

Pyridoxine was administred to four patients with parkinsonism who received maintenance doses of levodopa. Three reverted to more severe stages of parkinsonism, while the fourth had clearing of levodopa-induced side effects. There was an associated decrease of 60% or more in plasma dopa levels and in urinary excretion of dopa and dopamine in all subjects, while the excretion of dopac and HVA remained essentially unchanged. Pyridoxine thus appears to interfere with the therapeutic effect of levodopa in parkinsonism by increasing its rate of metabolism in the gastrointestinal tract or during absorption, making less available for transport to the brain.