スルファサラジン

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals -> Antibiotics

Pharmaceuticals -> Analgesics and anti-inflammatories

Pharmaceuticals -> Listed in ZINC15

2.65

0.6

203.9 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: APCI+; Dataset: TOXCAST; Source Identifier: DTXSID0021256]

199.36 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

200.4 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

199.7 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

Sulfasalazine

46.6

197.2

Maintenance therapy dosage for adults is 2 g daily.

Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 2000 mg/day, Lowest Therapeutic Dose (LTD): 25.0 mg/kg-day, and Screening Dose: 0.008 mg/kg-day.

10-Feb-21

The mode of action of sulfasalazine or its metabolites, 5-aminosalicylic acid and sulfapyridine, is still under investigation but may be related to the anti-inflammatory and/or immunomodulatory properties that have been observed in animal and <i>in vitro</i> models, to its affinity for connective tissue, and/or to the relatively high concentration it reaches in serous fluids, the liver, and intestinal walls, as demonstrated in autoradiographic studies in animals. In ulcerative colitis, clinical studies utilizing rectal administration of sulfasalazine, sulfapyridine, and 5-aminosalicylic acid have indicated that the major therapeutic action may reside in the 5-aminosalicylic acid moiety. The relative contribution of the parent drug and the major metabolites in rheumatoid arthritis is unknown.

Although the exact mechanism of action of sulfasalazine is not fully understood, it is thought to be mediated through the inhibition of various inflammatory molecules. Research have found that sulfasalazine and its metabolites, mesalazine and sulfapyridine, can inhibit leukotrienes and prostaglandins by blocking the cyclo-oxygenase and lipoxygenase pathway. Specific enzymes that were investigated include phospholipase A2, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX2), and arachidonate 5-lipoxygenase. Inhibitory activities on other non-arachidonic acid derivatives have also been observed, including PPAR gamma, NF-Kb, and IkappaB kinases alpha and beta.

The observed plasma half-life for intravenous sulfasalazine is 7.6 ± 3.4 hours.In fast acetylators, the mean plasma half-life of sulfapyridine is 10.4 hours while in slow acetylators, it is 14.8 hours.Due to low plasma levels produced by 5-aminosalicylic acid after oral administration, reliable estimates of plasma half-life are not possible.

In the intestine, sulfasalazine is metabolized by intestinal bacteria to sulfapyridine and 5-aminosalicylic acid. Of the two species, sulfapyridine is relatively well absorbed from the intestine and highly metabolized, while 5-aminosalicylic acid is much less well absorbed.Approximately 15% of a dose of sulfasalazine is absorbed as the parent drug and is metabolized to some extent in the liver to the same two species.Sulfapyridine can also be metabolized to 5-hydroxysulfapyridine and N-acetyl-5-hydroxy sulfapyridine. 5-aminosalicylic acid is primarily metabolized in both the liver and intestine to N-acetyl-5 aminosalicylic acid via a non-acetylation phenotype-dependent route.

Following oral administration of 1 g of sulfasalazine to 9 healthy males, less than 15% of a dose of sulfasalazine is absorbed as the parent drug. Detectable serum concentrations of sulfasalazine have been found in healthy subjects within 90 minutes after ingestion. Maximum concentrations of sulfasalazine occur between 3 and 12 hours post-ingestion, with the mean peak concentration (6 μg/mL) occurring at 6 hours.

Absorbed sulfapyridine and 5-aminosalicylic acid and their metabolites are primarily eliminated in the urine either as free metabolites or as glucuronide conjugates. The majority of 5-ASA stays within the colonic lumen and is excreted as 5-aminosalicylic acid and acetyl-5-aminosalicylic acid in the feces.

Following intravenous injection, the calculated volume of distribution for sulfasalazine was 7.5 ± 1.6 L.

The calculated clearance of sulfasalazine following intravenous administration was 1 L/hr. Renal clearance was estimated to account for 37% of total clearance.