Sulfasalazine
Sulfasalazine. Sulfonamide-mesalamine prodrug — gut bacteria cleave the azo bond releasing 5-ASA (anti-inflammatory, mesalamine-active… Oral half-life 7.6 h.
Sulfonamide-mesalamine prodrug — gut bacteria cleave the azo bond releasing 5-ASA (anti-inflammatory, mesalamine-active component) + sulfapyridine (mostly side-effect-driver). Used for IBD + rheumatoid arthritis (DMARD). PK (Azulfidine label, parent species): Absolute F < 15% for parent — most of a PO dose is cleaved by colonic bacteria to sulfapyridine (F 60%, well-absorbed) + 5-aminosalicylic acid (F 10–30%, poorly absorbed, locally active). Vdss 7.5 ± 1.6 L from IV data, t½ 7.6 ± 3.4 h. The "PK" recorded here is for the parent — the clinical effect is driven by 5-ASA topically in the colon for UC and by an undefined immunomodulatory mechanism for RA.
PK: EVERY STORED VALUE IS LABEL-DERIVED AND THE CITED PAPER SUPPORTS NONE OF THEM AND CONTRADICTS ONE. The volume and half-life are verbatim in the label and are explicitly INTRAVENOUS — "calculated volume of distribution (Vdss) for SSZ was 7.5 +/- 1.6 L" and "observed plasma half-life for intravenous sulfasalazine is 7.6 +/- 3.4 hours" — so class 6 is acquitted and pairing them with an independent bioavailability is correct. That bioavailability is the one contradiction: the label says "LESS THAN 15% for parent drug", an inequality stored as a point, and THE CITED ABSTRACT PUTS IT LOWER STILL at "3 to 12%", so the stored value sits ABOVE ITS OWN CITATION UPPER ENDPOINT. No primary publishes a point estimate and a midpoint of 3-12% is barred, so the number stays with its provenance corrected. A PHYSICAL CHECK PASSES: the record predicts 68.6 micromol/L against a verbatim "between ... 32 and 114 mumol/L", and bioavailability anywhere from 0.07 to 0.25 lands in range, SO THE F QUESTION IS INVISIBLE TO THE PHYSICAL TEST and is purely a provenance defect. THE ANALYTE QUESTION HAS AN UNUSUAL ANSWER AND THE RECORD ALREADY HANDLES IT: the systemically measurable species is the intact azo compound, which is NEITHER the colitis-active species, luminal 5-aminosalicylate, NOR the toxicity carrier, sulfapyridine. That is why this record is not local-acting. MY SUSPECTED TRANSPLANT WITH MESALAMINE RUNS THE OTHER WAY: mesalamine bioavailability of 0.25 is THIS record citation "at least 25% is absorbed".
Pharmacokinetics
- Oral — t½ 7.6 h · F 15% · ka 0.2754 h⁻¹ · Vd 7.5 L
Sources: PMID:2864155, PMID:2857146