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Pharmacology: Folic acid or folacin, is a member of the B vitamin group. It is involved in amino acid metabolism. Folic acid, in its reduced form, tetrahydrofolate, participates in many reactions involving one-carbon transfers. It is involved in the conversion of homocysteine to methionine and in the conversion of deoxyuridylate to thymidylate, an essential step required in the synthesis of DNA. As folic acid is necessary in the synthesis of DNA, it is essential in the formation of different body cells. Folic acid is necessary for the normal production and maturation of red blood cells. Deficiency of folic acid results in megaloblastic anemia.
Folic acid deficiency results in impaired processes of DNA synthesis, cellular replication and cell division. Cells with rapid turnover such as the red blood cells and the epithelial cells of the intestine may be readily affected. Deficiency of folic acid has been associated with birth defects (i.e. neural tube defects, congenital heart defects) certain cancers, blood disorders and higher risk of cardiovascular disorders as a result of homocystenemia. Folic acid participates in the conversion of homocysteine into methionine. When folic acid is deficient, homocysteine levels increase, a condition known as homocysteinemia. Folic acid supplementation is considered protective against such disorders. Results of clinical studies suggest that high doses of folic acid help reduce risk of birth defects, cardiovascular diseases and cancer.
Folic acid deficiency may result from inadequate dietary intake, impaired intestinal absorption secondary to gastrointestinal diseases, alcoholism and intake of drugs that inhibit folate absorption (i.e. anticonvulsants, phenytoin, oral contraceptives and methotrexate). Dietary deficiency is common in the elderly, malnourished and individuals who do not eat vegetables and fruits. Despite adequate dietary intake of folic acid, relative deficiency may be encountered in certain conditions where there are increased requirements for active DNA synthesis (such as pregnancy, and hematologic disorders).
In these circumstances, folic acid supplementation becomes important.
Pharmacokinetics: Folic acid is well absorbed in the gastrointestinal tract even in patients with malabsorption syndrome so parenteral administration is rarely necessary. In the presence of malabsorption syndrome, folic acid from oral supplements will still be absorbed, whereas absorption of folic acid from food sources may be impaired.
Pteroylglutamic acid is the common pharmacological form of folic acid. Following oral administration, folic acid is rapidly absorbed from the gastrointestinal tract, mainly from the proximal part (or from the duodenum). The naturally occurring folate polyglutamate or folic acid polyglutamates from food sources are enzymatically hydrolyzed to monoglutamate forms in the gastrointestinal tract prior to absorption.
The peak folate activity in blood after oral administration is within 30 to 60 minutes. Following absorption, pteroylglutamic acid is rapidly reduced to tetrahydrofolic acid. Therapeutically administered enters the portal circulation largely unchanged since it is a poor substrate for reduction by dihydrofolate reductase. Folic acid is converted to the metabolically active form 5-methyltetrahydrofolate in the plasma & liver. The liver is the principal storage site of folate. Folate is also actively concentrated in the CSF.
Folates are excreted in the urine and stool and are also destroyed by catabolism, so serum levels fall within a few days when intake is diminished. Because unaltered folic acid is readily and completely absorbed in the proximal jejunum.
Folate in excess of body requirements is excreted unchanged in the urine. Folate is distributed into breast milk. Haemodialysis removes folic acid.
