Tranexamic acid-hemostan

Tranexamic acid (generally marketed as Hemostan in Asia) is frequently approved for extreme bleeding. Hemostan 500mg is an anti fibrinolytic that effectively thwarts the launch of plasminogen to plasmin, a particle in charge for the dilapidation of fibrin. Fibrin is the fundamental structure for the development of a blood coagulates in hemostasis. It has approximately eight times the anti fibrinolytic action of an older analogue, -aminocaproic acid. Pharmacodynamics Pharmacokinetics Tranexamic acid (Hemostan 500mg) is an anti fibrinolytic agent that effectively thwarts breaking of fibrin coagulate. It inhibits joining of plasminogen and plasmin to fibrin, by this means stopping haemostatic plug termination. Absorption Riveted from the GI tract; peak plasma absorbtions after three hrs (when administered orally). Bioavailability: 30-50 percent, unaltered by food ingestion. Distribution It is broadly distributed all through the human body. Protein-binding: Very low. Transports over the placenta and disseminated into breast milk. Excretion Urine (discharged as unlatered drug); two hrs (elimination half-life). Tranexamic Acid Adverse Reactions Hemostan Side Effects Diarrhoea, vomiting, nausea, giddiness, disturbances in color vision, thromboembolic events, hypotension. Consult a doctor in case any of these side effects become persistent and problematic. These may not be the total possible side effects of Hemostan 500mg, consult your nearest healthcare service provider for further advice. Precautions Information Not Available

Special Precautions

Placid to temperate renal injury, uneven menstrual bleeding, haematuria, past recrod of thromboembolic disease. Observe intimately in dispersed intravascular coagulation. Monitor LFT and eye inspection recurrently throughout long-term use. Stop if disorder in color vision takes place. Keep away from IV injection rate less than 1 milliliter per minute due to hazard of hypotension. Pregnancy as well as lactation. Other Drug Interactions Information Not Available Other Interactions Information Not Available Food(before/after) Hemostan 500mg may be used with or without food but advisable to use after food to avoid GI troubles. Storage Intravenous Store at room temperature above 15 degree Celsius and below 30 degree celcisus. Keep away from direct light, heat and moisture. Oral Store at room temperature above 15 degree Celsius and below 30 degree celcisus. Keep away from direct light, heat and moisture. Keep away from the reach of children. Brand name: Hemostan, Fibrinon, Cyklokapron, Lysteda, Transamin Classification: Anti-fibrinolytic, antihemorrhagic Indications: Tranexamic acid is used for the prompt and effective control of hemorrhage in various surgical and clinical areas:

Treating heavy menstrual bleeding Hemorrhage following dental and/or oral surgery in patients with hemophilia Management of hemophilic patients (those having Factor VIII or Factor IX deficiency) who have oral mucosal bleeding, or are undergoing tooth extraction or other oral surgical procedures. Surgical: General surgical cases but most especially operative procedures on the prostate, uterus, thyroid, lungs, heart, ovaries, adrenals, kidneys, brain, tonsils, lymph nodes and soft tissues. Obstetrical and gynecological: abortion, post-partum hemorrhage and menometrorrahgia Medical: epistaxis, hemoptysis, hematuria, peptic ulcer with hemorrhage and blood dyscrasias with hemorrhage Effective in promoting hemostasis in traumatic injuries. Preventing hemorrhage after orthopedic surgeries.

Mechanism of Action Tranexamic acid is a synthetic derivative of the amino acid lysine. It exerts its antifibrinolytic effect through the reversible blockade of lysine-binding sites on plasminogen molecules. Antifibrinolytic drug inhibits endometrial plasminogen activator and thus prevents fibrinolysis and the breakdown of blood clots. The plasminogen-plasmin enzyme system is known to cause coagulation defects through lytic activity on fibrinogen, fibrin and other clotting factors. By inhibiting the action of plasmin (finronolysin) the anti-fibrinolytic agents reduce excessive breakdown of fibrin and effect physiological hemostasis. Contraindications 1. Allergic reaction to the drug or hypersensitivity 2. Presence of blood clots (eg, in the leg, lung, eye, brain), have a history of blood clots, or are at risk for blood clots 3. Current administration of factor IX complex concentrates or anti-inhibitor coagulant concentrates Precautions 1. Pregnancy. Tranexamic acid crosses the placenta. 2. Lactation. Tranexamic acid is distributed into breast milk; concentrations reach approximately 1% of the maternal plasma concentration. 3. Contraceptives, estrogen-containing, oral or Estrogens. Concurrent use with tranexamic acid may increase the potential for thrombus formation. 4. Renal function impairment (medication may accumulate; dosage adjustment based on the degree of impairment is recommended) 5. Hematuria of upper urinary tract origin (risk of intrarenal obstruction secondary to clot retention in the renal pelvis and ureters if hematuria is massive; also, if hematuria is associated with a disease of the renal parenchyma, intravascular precipitation of fibrin may occur and exacerbate the disease)

Nursing Responsibilities 1. Unusual change in bleeding pattern should be immediately reported to the physician. 2. For women who are taking Tranexamic acid to control heavy bleeding, the medication should only be taken during the menstrual period. 3. Tranexamic Acid should be used with extreme caution in CHILDREN younger than 18 years old; safety and effectiveness in these children have not been confirmed. 4. The medication can be taken with or without meals. 5. Swallow Tranexamic Acid whole with plenty of liquids. Do not break, crush, or chew before swallowing. 6. If you miss a dose of Tranexamic Acid, take it when you remember, then take your next dose at least 6 hours later. Do not take 2 doses at once. 7. Inform the client that he/she should inform the physician immediately if the following severe side effects occur:

Severe allergic reactions such as rash, hives, itching, dyspnea, tightness in the chest, swelling of the mouth, face, lips or tongue Calf pain, swelling or tenderness Chest pain Confusion Coughing up blood Decreased urination Severe or persistent headache Severe or persistent body malaise Shortness of breath Slurred speech Slurred speech Vision changes

Ketorolac-analac
Ketorolac tromethamine (KT), a potent non-narcotic analgesic, with cyclooxygenase inhibitory activity, was administered (14C-labeled and unlabeled) intravenously (iv), orally (po), and intramuscularly (im) in solution to humans, cynomolgus monkeys, rabbits, rats, and mice. KT was absorbed rapidly (Tmax less than 1.0 hr) and efficiently (greater than 87%) following po and im doses in all species. The plasma halflife of ketorolac (K) ranged from 1.1 hr (rabbits) to 6.0 hr (humans). The protein binding of K ranged from 72.0% (mouse) to 99.2% (humans). Linear pharmacokinetics of K was observed in the mouse after single oral doses of KT ranging from 0.25 to 16 mg/kg. Radioactivity was excreted predominantly into urine, ranging from 78.9% (mouse) to 102% (monkey) following iv doses. The dose was excreted into urine primarily as K conjugates, K, and p-hydroxy-K in humans. The monkey was similar to humans with respect to kinetics, but did not form the p-hydroxy metabolite. The rabbit was unusual in that it exhibited substantial presystemic metabolism (50%). The rat excreted a much higher percentage of radioactivity into the feces and formed an additional unidentified metabolite. The most comparable species with respect to humans metabolically was the mouse. The metabolism and excretion of K was similar following iv, po, and im doses within each species studied.

Pharmacokinetics Ketorolac tromethamine is a racemic mixture of [-]S- and [+]R-enantiomeric forms, with the Sform having analgesic activity.
Comparison of IV, IM and Oral Pharmacokinetics

The pharmacokinetics of ketorolac tromethamine, following IV and IM doses of ketorolac tromethamine and oral doses of TORADOL (ketorolac tromethamine) , are compared in Table 1. In adults, the extent of bioavailability following administration of the ORAL form of TORADOL and the IM form of ketorolac tromethamine was equal to that following an IV bolus.
Linear Kinetics

In adults, following administration of single ORAL doses of TORADOL or IM or IV doses of ketorolac tromethamine in the recommended dosage ranges, the clearance of the racemate does not change. This implies that the pharmacokinetics of ketorolac tromethamine in adults, following single or multiple IM or IV doses of ketorolac tromethamine or recommended oral doses of TORADOL (ketorolac tromethamine) , are linear. At the higher recommended doses, there is a proportional increase in the concentrations of free and bound racemate.
Absorption

TORADOL (ketorolac tromethamine) is 100% absorbed after oral administration (see Table 1). Oral administration of TORADOL (ketorolac tromethamine) after a high-fat meal resulted in

decreased peak and delayed time-to-peak concentrations of ketorolac tromethamine by about 1 hour. Antacids did not affect the extent of absorption.
Distribution

The mean apparent volume (V) of ketorolac tromethamine following complete distribution was approximately 13 liters. This parameter was determined from single-dose data. The ketorolac tromethamine racemate has been shown to be highly protein bound (99%). Nevertheless, plasma concentrations as high as 10 g/mL will only occupy approximately 5% of the albumin binding sites. Thus, the unbound fraction for each enantiomer will be constant over the therapeutic range. A decrease in serum albumin, however, will result in increased free drug concentrations. Ketorolac tromethamine is excreted in human milk (see PRECAUTIONS: Nursing Mothers).
Metabolism

Ketorolac tromethamine is largely metabolized in the liver. The metabolic products are hydroxylated and conjugated forms of the parent drug. The products of metabolism, and some unchanged drug, are excreted in the urine.
Excretion

The principal route of elimination of ketorolac and its metabolites is renal. About 92% of a given dose is found in the urine, approximately 40% as metabolites and 60% as unchanged ketorolac. Approximately 6% of a dose is excreted in the feces. A single-dose study with 10 mg TORADOL (ketorolac tromethamine) (n=9) demonstrated that the S-enantiomer is cleared approximately two times faster than the R-enantiomer and that the clearance was independent of the route of administration. This means that the ratio of S/R plasma concentrations decreases with time after each dose. There is little or no inversion of the R- to S- form in humans. The clearance of the racemate in normal subjects, elderly individuals and in hepatically and renally impaired patients is outlined in Table 2 (see CLINICAL PHARMACOLOGY: Kinetics in Special Populations). The half-life of the ketorolac tromethamine S-enantiomer was approximately 2.5 hours (SD 0.4) compared with 5 hours (SD 1.7) for the R-enantiomer. In other studies, the half-life for the racemate has been reported to lie within the range of 5 to 6 hours.
Accumulation

Ketorolac tromethamine administered as an IV bolus every 6 hours for 5 days to healthy subjects (n=13), showed no significant difference in Cmax on Day 1 and Day 5. Trough levels averaged 0.29 g/mL (SD 0.13) on Day 1 and 0.55 g/mL (SD 0.23) on Day 6. Steady state was approached after the fourth dose. Accumulation of ketorolac tromethamine has not been studied in special populations (geriatric, pediatric, renal failure or hepatic disease patients).
Ketorolac is a new chiral nonsteroidal anti-inflammatory drug (NSAID) which is marketed for analgesia as the racemate. The drug is administered as the water soluble tromethamine salt and is available in

tablets or as an intramuscular injection. The absorption of ketorolac is rapid, Cmax being attained between 20 to 60 min. Its oral bioavailability is estimated to range from 80 to 100%. The drug is extensively bound (> 99%) to plasma proteins and has a volume of distribution (0.1 to 0.3 L/kg) comparable with those of other NSAIDs. Only small concentrations of ketorolac are detectable in umbilical vein blood after administration to women in labour. The elimination half-life is between 4 and 6h and is moderate in comparison with other NSAIDs. The area under the plasma concentration-time curve of ketorolac is proportional to the dose after intramuscular administration of therapeutic doses to young healthy volunteers. Ketorolac is extensively metabolised through glucuronidation and oxidation; little if any drug is eliminated unchanged. Most of the dose of ketorolac is recovered in the urine as conjugated drug. Although ketorolac is excreted into the breast milk, the amount of drug transferred comprises only a small fraction of the maternal exposure. Little stereoselectivity was present in the pharmacokinetics of ketorolac in a healthy volunteer receiving single intravenous or oral doses. The elderly exhibit reduced clearance of the drug. Renal insufficiency appears to cause an accumulation of ketorolac in plasma, although hepatic disease may not affect the pharmacokinetics. Absorption

Bioavailability Rapidly and completely absorbed following IM administration.1 2 36 37 38 140 173 Rapid and almost completed absorbed following oral administration; 1 2 36 37 38 70 95 173 bioavailability reported to be 80100%.1 2 36 37 38 70 95 173 Onset IM administration: Onset in 10 minutes, with peak analgesia at 75150 minutes.1 47 50 51 53 Oral administration: Onset in 3060 minutes, with peak analgesia at 1.54 hours.55 56 57 58 59 60 61
137 138

Duration Oral or IM administration: 68 hours.47 50 51 53 55 56 57 58 59 60 61 137 138 Food Food decreases rate but not extent of absorption.1 2 70 83 Special Populations Rate of absorption from GI tract may be decreased in patients with hepatic43 70 or renal44 70 impairment and in geriatric individuals.43 70

Distribution

Extent Not distributed widely.1 2 37 70 140 Crosses the blood-brain barrier poorly.1 91 Crosses the placenta;1 2 41 65 91 173 distributed into milk.1 40 70 91 92 Plasma Protein Binding >99%.1 2 37 38 70
Elimination

Metabolism Metabolized in the liver by hydroxylation; 1 91 also undergoes conjugation with glucuronic acid.1
37 38 173

Elimination Route Excreted in urine (92%) as parent drug (60%) or metabolites (40%) and in feces (6%).1 38 70 173 Half-life 46 hours in adults;1 2 36 37 38 70 80 91 97 140 173 3.86.1 hours in pediatric patients.1 173 197 Special Populations Hepatic impairment (e.g., cirrhosis) does not appear to substantially affect half-life.1 2 43 173 In patients with cirrhosis, half-life of about 4.55.4 hours reported.1 43 91 173 Renal impairment: Half-life is about 910 hours (range: 3.219 hours);1 2 44 91 173 in patients undergoing dialysis, half-life of about 13.6 hours (range: 839.1 hours) reported.1 Geriatric individuals: Half-life is about 57 hours (range: 4.38.6 hours).1 2 42 70 80 91 173

Diflosid-diclofenac
Diclofenac sodium was administered as 50 mg tablets to four healthy male volunteers in a two-way randomized crossover study in which volunteers were either fasted or were given a standard breakfast immediately prior to dosing. Blood samples were obtained upto 9 hours period and drug concentration were determined by HPLC method. Besides a significantly delayed (at p > 0.1) peak in fed state; an increase in absorption rate constant was observed as the only significant (at p > 0.05) effect of food on biopharmaceutic characteristic of diclofenac sodium. However, the intrinsic absorption of diclofenac sodium is also fast and it is not being the rate limiting factor in the bioavailability of diclofenac sodium, its decrease upto about 18 minutes (0.31 +/- 0.05 hr) from 11 minutes (0.19 +/- 0.02 hr) produces a null difference as the net effect on bioavailability, particularly when the drug is to be used in multiple dosage regimen. Pharmacokinetics: Absorption: In humans, orally-administered diclofenac sodium is rapidly and almost completely absorbed and distributed to blood, liver, and kidneys. The plasma concentrations show a linear relationship to the amount of drug administered. No accumulation occurs provided the recommended dosage intervals are observed. Enteric coating may delay the onset of absorption from 25 and 50 mg tablets. Absorption occurs more rapidly when the drug is administered on an empty stomach (Tmax 2.5 hours), than with meals (Tmax 6 hours). The bioavailability remains the same under both conditions. The mean peak plasma concentration of 1.5 g/mL (5 mol/L) is attained, on average, 2 hours after ingestion of one 50 mg enteric-coated tablet. Following administration of slow-release (SR) diclofenac sodium, Cmax is reached at approximately 4 hours or later. Significant drug plasma concentrations persist when levels would have dropped almost to baseline values following enteric-coated tablet administration. Mean plasma concentrations of 13 ng/mL (40 nmol/L) were produced 24 hours after diclofenac sodium slow release 100 mg, or 16 hours after diclofenac sodium slow release 75 mg (single dose). Trough levels are approximately 22 to 25 ng/mL (70 to 80 nmol/L) during treatment with diclofenac sodium slow release 100 mg once daily or diclofenac sodium slow release 75 mg twice daily. In pharmacokinetic studies no accumulation of diclofenac sodium was found following repeated once daily administration of diclofenac sodium slow release 100 mg tablets or repeated twice daily administration of diclofenac sodium slow release 75 mg tablets. Suppositories have a more rapid onset, but slower rate of absorption than oral enteric-coated tablets. Cmax is approximately 2/3 of that produced by an equivalent 50 mg enteric-coated tablet oral dose. Tmax occurs within 1 hour. The unchanged diclofenac plasma AUC values for rectal administration are within the range of values produced by equivalent oral enteric-coated tablet doses. Since about half the active substance is metabolized during its first passage through the liver ("first pass" effect), the area under the concentration curve (AUC) following oral or rectal administration is about half as large as it is following a parenteral dose of equal size.

Distribution: Diclofenac sodium is extensively bound (99%) to serum albumin. The apparent volume of distribution is 0.12 to 0.17 L/kg. Single-dose (oral or i.m.) studies in rheumatoid patients with joint effusions have shown that diclofenac is distributed to the synovial fluid, where Tmax occurs 2 to 4 hours after plasma Tmax. Synovial fluid concentrations exceed plasma levels within 4 to 6 hours of administration. This elevation above plasma concentrations can be maintained for up to 12 hours. The synovial fluid elimination half-life is at least 3 times greater than that for plasma. Biotransformation: Diclofenac undergoes single and multiple hydroxylation and methoxylation, producing 3'-, 4'-, 5-hydroxy, 4'-5-hydroxy and 3'-hydroxy-4'-methoxy derivatives of diclofenac. These phenolic metabolites are largely inactive, and (along with the parent compound) are mostly converted to glucuronide conjugates. Elimination: Plasma clearance of diclofenac is 26356 mL/minute. The mean terminal drug half-life in plasma is 1.8 hours after oral doses. In humans about 60% of the drug and its metabolites are eliminated in the urine and the balance through bile in the feces. More than 90% of an oral dose is accounted for in elimination products within 72 hours. About 1% of an oral dose is excreted unchanged in urine.

Zegen-cefuroxime

Pharmacokinetics: Cefuroxime is administered intravenously and intramuscularly as the sodium salt and orally as cefuroxime axetil. Approximately 3350% of the circulating cefuroxime is protein-bound. It is distributed into most body tissues and fluids including gallbladder; liver; kidney; bone; uterus; ovary; sputum; bile; and peritoneal, pleural, and synovial fluids. It penetrates inflamed meninges and reaches therapeutic levels within the CSF. It does cross the placenta. Cefuroxime is largely excreted unchanged into the urine via glomerular filtration and tubular secretion. A small percentage is excreted in breast milk. The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Elimination halflife is 12 hours in patients with normal renal function. The axetil portion of cefuroxime axetil is metabolized to acetic acid and acetaldehyde.

Absorption
Bioavailability Following oral administration of cefuroxime axetil, the drug is absorbed from the GI tract as the 1-(acetyloxy)ethyl ester and rapidly hydrolyzed to cefuroxime.79 82 92 93 97 98 99 104 105 106 107 108 Cefuroxime axetil has little, if any, microbiologic activity until hydrolyzed in vivo to cefuroxime. 82 116 Oral suspension is not bioequivalent to tablets.79 215 In adults receiving film-coated tablets, peak serum concentrations attained approximately 23 hours after the dose.79 81 Following oral administration of the oral suspension given with milk or milk products in children, peak serum concentrations attained within 2.73.6 hours.79 148 Cefuroxime sodium not appreciably absorbed from the GI tract; must be given parenterally.1 2 6 21 30Following IM administration in healthy adults, peak serum concentrations attained within 1560 minutes.1 2 3 6 21 30 In women, serum cefuroxime concentrations are lower when IM injections are given into the gluteus maximus rather than into the thigh.30 Food

In adults, bioavailability following oral administration of film-coated tablets averages about 37% when given in the fasting state and 52% when given with or shortly after food.79 81 Absorption increased when cefuroxime axetil given with milk or infant formula.98 The extent (but not rate) of absorption is substantially greater when administered concomitantly with milk compared with applesauce or fasting.98

Distribution
Extent Following IM or IV administration, widely distributed into body tissues and fluids including pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor.1 Therapeutic concentrations may be attained in CSF following IV administration in patients with inflamed meninges.2 3 7 18 22 26 29 30 43 Readily crosses the placenta1 2 24 and is distributed into milk.1 Plasma Protein Binding 3350%.1 2 6 21 30 79

Elimination
Metabolism Following oral administration, cefuroxime axetil rapidly hydrolyzed to cefuroxime by nonspecific esterases in the intestinal mucosa and blood.79 82 92 93 97 98 99 104 105 106 107 108 Cefuroxime not metabolized.2 6 21 27 30 Elimination Route Eliminated unchanged principally in urine.2 6 21 27 30 Half-life Adults: 1.21.6 hours following oral administration79 81 98 and 12 hours following IV or IM administration.1 3 18 21 27 30 Neonates and children: Half-life inversely proportional to age.6 25 30

Advice to Patients

Advise patients that antibacterials (including cefuroxime) should only be used to treat bacterial infections; they do not treat viral infections (e.g., the common cold).1 79 214 Importance of completing full course of therapy, even if feeling better after a few days.1 79 214

Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with cefuroxime or other antibacterials in the future.1 79 214 Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.1 79 214 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.1 79 214 Advise individuals with phenylketonuria and other individuals who must restrict their intake of phenylalanine that Ceftin oral suspensions contain aspartame (NutraSweet), which is metabolized in the GI tract to phenylalanine.79 Importance of informing clinicians if an allergic reaction occurs.1 79 214 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 79 214 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.1 79 214 Importance of informing patients of other important precautionary information. 1 79 214 (See Cautions.)

Dazomet-metronidazole
Pharmacokinetics Dazomet is practically not absorbed from the gastrointestinal tract. The plasma protein binding is 90%. This medication is distributed unevenly in organs and accumulates in adipose tissue, liver, and larvae of helminths. Mebendazole is metabolized in the liver to 2-amino derivative. T1/2 is 2.5-5.5 hours. More than 90% of the dose is excreted unchanged in feces. Grown deep portion (5-10%) is excreted by kidneys.

Absorption, Distribution & Excretion: One hr after oral administration to rats, unhydrolyzed mylone was found in stomach. Carbon disulfide equiv to 1-3% of dose was found in stomach and 1.5% of dose was found in exhaled air. After either intravenous or oral administration of mylone to dogs, carbon disulfide was found in exhaled air...
[Menzie, C.M. Metabolism of Pesticides. U.S. Department of the Interior, Bureau of Sport Fisheries and Wildlife, Publication 127. Washington, DC: U.S. Government Printing Office, 1969., p. 255] **PEER REVIEWED**

Not

readily

absorbed

by

the

skin.

[Spencer, E. Y. Guide to the Chemicals Used in Crop Protection. 7th ed. Publication 1093. Research Institute, Agriculture Canada, Ottawa, Canada: Information Canada, 1982., p. 159] **PEER REVIEWED**

In a rat metabolism study, dazomet, metam sodium, and MITC were tested at two dose levels. All three were excreted mainly in urine with small amounts excreted in feces. Three different compounds (MITC, carbon dioxide [CO2], carbon oxide sulfide [COS]/carbon disulfide [CS2]) were found to be excreted in the lungs over a 73 hour collection period. There were no differences between males and females in amounts excreted via the three excretion routes; however, tissue and plasma levels, and plasma area under the curves (AUCs) were consistently higher in females than in males. It should be noted that these differences were approximately 2-fold or less. All three compounds were rapidly absorbed from the GI tract. High uptake was seen in the liver, kidneys, and lung, with the lowest level in testes, brain and eyes. Metabolic profiles detected in urine, liver, and kidneys were basically similar for the three compounds but there were some differences, mainly quantitative in nature.
[USEPA/Office of Pesticide Programs; Revised HED Human Health Risk Assessment For Phase 3 p.14 EPA-HQ-OPP-2005-0128-0003 (June 2005). Available from, as of October 23, 2008:http://www.regulations.gov/search/Regs/home.html#home **PEER REVIEWED**

Folic-acid-stresstabs

Pharmacokinetics: Folic acid polyglutamates from food sources are enzymatically hydrolyzed in the gastrointestinal tract to monoglutamates prior to absorption, which occurs mainly in the proximal small intestine. 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. Following absorption of 1 mg or less, folic acid is converted in the liver and plasma to its metabolically active form tetrahydrofolic acid, which is then distributed into all body tissues. Normal serum folate concentrations range from 0.016 to 0.021 g/mL. The liver contains about 50% of total body folate stores. Larger doses of folic acid may escape metabolism by liver and appear in the blood mainly as folic acid. Following oral administration of single 0.1 to 0.2 mg doses of folic acid in healthy adults, only a trace amount of the drug appears in urine. Following administration of large doses, the renal tubular reabsorption maximum is exceeded, and excess folate is excreted unchanged in urine. After doses of about 2.5 to 5 mg, about 50% of a dose is excreted in urine and after a 15 mg dose, up to 90% may be recovered in urine. Small amounts of orally administered folic acid have been recovered from feces. Indications: Folic acid is used in the treatment of megaloblastic and macrocytic anemias caused by folate deficiency. It is also used in the treatment of megaloblastic anemias of pregnancy, infancy and childhood, as well as megaloblastic anemias associated with primary liver disease, alcoholic cirrhosis, intestinal strictures, anastomoses or sprue. In large doses, folic acid is used in the treatment of tropical sprue. There is strong evidence that prophylactic therapy with folic acid, prior to and during pregnancy, can reduce the risk of fetal neural tube defects. Expert groups recommend that all women of child bearing potential, whether planning pregnancy or not, should maintain an adequate daily intake of folic acid (see Dosage). Folic acid is not effective in reversing the effects of folic acid reductase inhibitors such as methotrexate, for which leucovorin calcium (folinic acid) must be used. [

Pharmacokinetics Human pharmacokinetic studies indicate folic acid has very high bioavailability, with large oral doses of

folic acid substantially raising plasma levels in healthy subjects in a time- and dose-dependent manner. Subsequent to high-dose oral administration of folic acid (ranging from 25-1,000 mg/day), red blood cell (RBC) folate levels remain elevated for periods in excess of 40 days following discontinuation of the supplement. Folic acid is poorly transported to the brain and rapidly cleared from the central nervous system. The primary methods of elimination of absorbed folic acid are fecal (through bile) and urinary. After ingestion, the process of conversion of folic acid to the metabolically active coenzyme forms is relatively complex. Synthesis of the active forms of folic acid requires several enzymes, adequate liver and intestinal function, and adequate supplies of riboflavin (B2), niacin (B3), pyridoxine (B6), zinc, vitamin C, and serine. After the formation of the coenzyme forms of the vitamin in the liver, these metabolically active compounds are secreted into the small intestine with bile (the folate enterohepatic cycle), where they are reabsorbed and distributed to tissues throughout the body. Despite the biochemical complexity of this process, evidence suggests oral supplementation with folic acid is able to increase the bodys pool of the active reduced folate metabolites (such as methyltetrahydrofolate) in healthy individuals.

5 Enzyme defects, malabsorption or digestive system pathology, and liver disease can result in impaired ability to activate folic acid to the required coenzyme forms in the body. Evidence indicates some individuals have a severe methyltetrahydrofolate reductase, congenital deficiency of the enzyme

which is needed to convert folic acid to the 5-methyltetrahydrofolate coenzyme form of the vitamin. The existence of milder forms of this enzyme defect is strongly suspected and likely interacts with dietary folate status to determine risk for some disease conditions. 6-10 In individuals with a genetic defect of this enzyme (whether mild or severe), greater dietary exposure to foods rich in folates and supplemental folates in the form of folinic acid or 5-methyltetrahydrofolate might be preferable to folic acid supplementation.
Folic Acid See Introduction

PharmacoKinetics

Oral absorption of Folic Acid is found to be 75% 5. Plasma protien binding is 70%. Renal Excretion accounts for major and plasma half life is short.