4-アミノサリチル酸

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Listed in ZINC15

LogP= 1.32

1.6

MINUTE CRYSTALS FROM ALC

WHITE, OR NEARLY WHITE, BULKY POWDER

NEEDLES, PLATES FROM ALC-ETHER

A reddish-brown crystalline powder is obtained on recrystallization from ethanol-ether.

1 G SOL IN ABOUT 7 ML WATER; SLIGHTLY SOL IN ALC /CALCIUM SALT/

PH OF 1% SOLN: ABOUT 7; FREELY SOL IN WATER /POTASSIUM SALT/

For more Solubility (Complete) data for P-AMINOSALICYLIC ACID (7 total), please visit the HSDB record page.

SOL IN DILUTE NITRIC ACID & DILUTE SODIUM HYDROXIDE

Virtually insoluble in benzene, choroform, or carbon tetrachloride

Breast Feeding; Lactation; Milk, Human; Anti-infective Agents; Antitubercular Agents

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

150-151 °C, with effervescence

NEEDLES FROM ALC; MP: 115 °C /ETHYL ESTER/

150.5 °C

White or nearly white solid; Affected by light and air; [Hawley] Beige powder; [MSDSonline]

Solid

Warning

H315 (43.5%): Causes skin irritation [Warning Skin corrosion/irritation]

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 69 reports by companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Status: Active Update: 23-11-2022 https://echa.europa.eu/registration-dossier/-/registered-dossier/25234

Benzoic acid, 4-amino-2-hydroxy-: Does not have an individual approval but may be used under an appropriate group standard

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

A review of the literature on the clinical experience, tolerance and toxicity of mesalamine (5-aminosalicylic acid), aminosalicylic acid (4-aminosalicylic acid) and newer mesalamine based drugs for the treatment of chronic inflammatory bowel disease is presented.[Jarnerot G; Drugs 37 (Jan): 73-86 (1989)]

The initial therapy and retreatment of pulmonary tuberculosis as well as various complicating factors that may affect treatment decisions are presented. Chemotherapeutic agents used in the treatment of tuberculosis and their dosage regiments are mentioned including isoniazid, ethambutol, rifampin, pyrazinamide, ethionamide, cycloserine, streptomycin, kanamycin, aminosalicylate (aminosalicylic acid), and capreomycin.[Spagnolo SV; Drug Therapy 15 (Nov): 91-92, 97-100 (1985)]

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

...PARA-AMINOSALICYLIC ACID.../INHIBITS METABOLISM OF CHLORAMPHENICOL/

PENTOBARBITAL /SRP: CNS DEPRESSION/ IN MICE WAS ENHANCED AFTER PRE-TREATMENT WITH... P-AMINOSALICYLIC ACID. INCR /SRP: CNS DEPRESSION/ APPEARED TO BE DUE TO RELEASE OF PENTOBARBITAL FROM SERUM-PROTEIN BINDING, RESULTING IN HIGHER CEREBRAL CONCN...

ADDITIVE & SYNERGISTIC WITH STREPTOMYCINS & ISONIAZID.

Probenecid decreases the renal excretion of this agent.

For more Interactions (Complete) data for P-AMINOSALICYLIC ACID (19 total), please visit the HSDB record page.

SEVERE THERAPEUTIC MISADVENTURES, ALTHOUGH RARE, HAVE INCL...HEPATITIS...METHEMOGLOBINEMIA...

Adequate and well-controlled studies in humans have not been done. In one study, an increased malformation rate for ears and limbs, and hypospadias were reported in infants of patients taking aminosalicylates with other antitubercular medications. However, other studies have not found aminosalicylates to be teratogenic. /Aminosalicylates/

The literature has been reviewed for contact dermatitis occurring to antituberculosis agents. Of the 12 known drugs, 6 (isoniazid, rifampicin, ethambutol, p-aminosalicylic acid, streptomycin and kanamycin) have been documented by patch test to cause this type of dermatitis in certain individuals.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Aminosalicylic acid

vMOST-DILI-concern

5

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

An N-acetylation polymorphism is described that is expressed toward arylamine carcinogens in tumor target organs of an inbred rat model. High levels ... of arylamine carcinogen N-acetyltransferase activity were observed in kidney, colon, prostate and urinary bladder cytosols derived from Fischer (F-344) inbred rats ... Significantly lower ... levels of arylamine carcinogen N-acetyltransferase activity were observed for corresponding tissue cytosols derived from Wistar-Kyoto inbred rats. Intermediate levels of arylamine carcinogen N-acetyltransferase activity significantly different from both the parental strains were observed in F1 hybrids of the parental strains, consistent with codominant expression of two alleles at a single gene locus. The arylamine substrates exhibiting the acetylator phenotype-dependent N-acetyltransferase activities included ... p-aminosalicylic acid ... Highest levels of arylamine carcinogen N-acetyltransferase were expressed consistently in colon cytosol, but expression of the N-acetylation polymorphism toward arylamine carcinogens was observed in each (kidney, colon, prostate and urinary bladder) of the tumor target organs. The expression of the N-acetylation polymorphism in tumor target organs suggests that the inbred rat model will be useful in assessing the role of acetylator phenotype in arylamine-induced cancers of the colon and prostate.

An overview is presented of a selected number of mono-aromatic derivatives and their short-term effects on hepatic fatty acid biosynthesis. The cmpd discussed in this paper are o-hydroxybenzoate ... m-hydroxybenzoate, p-hydroxybenzoate, benzoate, p-t-butylbenzoate, p-aminosalicylate, clofibrate, halofenate, alpha-cyano-4-hydroxycinnamate and benfluorex. All of these drugs inhibit fatty acid biosynthesis by isolated rat liver cells, albeit with different effectiveness. In contrast, the cmpd have differential effects on fatty acid esterification and oxidation by isolated hepatocytes. An attempt is made to describe in molecular terms the underlying mechanisms of the acute inhibitory effects of the mono-aromatic derivatives on hepatic lipogenesis. It is proposed that all of the drugs exert an inhibitory action at the level of acetyl-CoA carboxylase, the enzyme generally considered to catalyze the rate-limiting step in hepatic fatty acid synthesis. This inhibitory effect may be either direct, i.e. by an alteration of the enzyme's structure as a results of interaction between drug and enzyme, or indirect, i.e. through a drug-induced change in the cellular levels of allosteric effectors of acetyl-CoA carboxylase.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

Aminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic against <i>Mycobacterium tuberculosis</i> (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid.

There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against <i>Mycobacterium tuberculosis</i>. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by <i>M. tuberculosis</i>.

The antimicrobial activity of aminosalicylic acid is highly specific, and microorganisms other than Mycobacterium tuberculosis are unaffected. Most nontuberculous mycobacteria are not inhibited by the drug.

Aminosalicyclic acid is a structural analog of paraaminobenzoic acid, and its mechanism of action appears to be very similar to that of the sulfonamides. Since the sulfonamides are ineffective against Mycobacterium tuberculosis, and aminosalicyclic is inactive against sulfonamide susceptible bacteria, it is probable that the enzymes responsible for folate biosynthesis in various microorganisms may be quite exacting in their capacity to distinguish various analogs from the true metabolite.

Hepatic.

ACETYLATION IS MAJOR ROUTE FOR INACTIVATION OF MANY DRUGS SUCH AS ... P-AMINOSALICYLIC ACID... ENZYMES WHICH CATALYSE THESE REACTIONS, ACETYL COENZYME A:N-ACETYLTRANSFERASES (EC2.3.1.5), ARE LOCATED IN LIVER CYTOSOL.

WHEN ADMIN ORALLY TO MAN IT IS RAPIDLY ABSORBED, & IS EXCRETED IN URINE AS UNCHANGED P-AMINOSALICYLIC ACID & AS ACETYL GLUCURONYL, GLYCYL & GLUTAMINYL CONJUGATES.

YIELDS 5-AMINO-2-CARBOXYPHENYL-BETA-D-GLUCURONIDE IN MAN. 4-AMINOCATECHOL IN PSEUDOMONAS. 4-AMINOSALICYLOYLGLUTAMINE & 4-AMINOSALICYLOYLGLYCINE IN MAN. /TABLE/

Blood from tuberculosis patients was cultured before, during, and after withdrawal of therapy involving five different drug combinations if isoniazid, thiacetazone, p-aminosalicyclic acid, and streptomycin. The approaches used to detect DNA damage were chromosome aberrations and sister chromatid exchanges (SCEs). A total of 179 subjects were analyzed. In combo these drugs showed synergistic, additive, and antagonistic effects, though they were found to be nonclastogenic individually. Four of the drug combinations, isoniazid plus thiacetazone, isoniazid plus p-aminosalicyclic acid, isoniazid plus thiacetazone plus streptomycin, and isoniazid plus p-aminosalicyclic acid plus streptomycin, induced a significant incr in the frequency of aberrations, whereas isoniazid plus streptomycin did not induce aberrations. In fact, streptomycin appeared to reduce the frequency of aberrations. SCEs were incr in only two patients: one treated with isoniazid plus thiacetazone and the other with isoniazid plus p-aminosalicyclic acid. The frequency of aberrations after withdrawal of therapy was decr; it was slightly higher than the controls, though it was insignificant. The return to normalcy could be due to elimination of damaged cells or the repair of DNA in lymphocytes. Though the drug-induced aberrations do not persist after withdrawal of therapy, the chromosome damaging combo of drugs should be used with caution, because the possibility of meiotic chromosome damage in germ cells (during therapy), which might be passed on to the next generation, cannot be ruled out.

For more Metabolism/Metabolites (Complete) data for P-AMINOSALICYLIC ACID (9 total), please visit the HSDB record page.

Drugs used in the treatment of tuberculosis. They are divided into two main classes: first-line agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and second-line drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.

BIOAVAILABILITY STUDIES ON P-AMINOSALICYLIC ACID & ITS SALTS IN 12 SUBJECTS. COLORIMETRIC ASSAY INDICATED THAT PEAK BLOOD LEVELS OCCURRED @ 0.5, 0.75, 1.5, & 3 HR FOR SODIUM, POTASSIUM, & CALCIUM SALTS & P-AMINOSALICYLIC ACID, RESPECTIVELY.

URINE EXCRETION DATA SHOWED ABSORPTION TO BE ESSENTIALLY COMPLETE ALTHOUGH RATES OF ABSORPTION DIFFERED.

Aminosalicyclic acid is readily absorbed from the gastrointestinal tract. A single oral dose of 4 g of the free acid produces maximal concentrations in plasma of about 75 ug/ml within 1.5 to 2 hours. The sodium salt is absorbed even more rapidly. The drug appears to be distributed throughout the total body water and reaches high concentrations in pleural fluid and caseous tissue. However, values in CSF are low, perhaps because of active outward transport.

Over 80% of the drug is excreted in the urine; more than 50% is in the form of the acetylated compound. The largest portion of the remainder is made up of the free acid.

For more Absorption, Distribution and Excretion (Complete) data for P-AMINOSALICYLIC ACID (8 total), please visit the HSDB record page.

Used as an industrial preservative, a chemical intermediate, and an antitubercular drug; [HSDB]

Industrial preservative.

Used as a chemical intermediate for the synthesis of bromopride; metoclopramide; xipamide

MEDICATION (VET)

MEDICATION

PREPD BY HEATING M-AMINOPHENOL WITH AMMONIUM CARBONATE OR POTASSIUM BISCARBONATE IN SOLN UNDER PRESSURE. PREPN FROM SODIUM P-AMINOSALICYLATE.

Derivation: From m-aminophenol and potassium bicarbonate, soluble under pressure.

USP

Available commercially as the free acid and as the sodium dihydrate salt.