Is Plasma Level Monitoring of Sulfasalazine Indicated in the Treatment of Crohn's Disease or Ulcerative Colitisquest;

摘要

Following a single oral dose of 1.25 g sulfapyridine (SP), the pharmacokinetic properties of this moiety of sulfasalazine were evaluated in healthy volunteers. While there was no difference in the absorption characteristics, plasma protein binding (49.6 plusmn; 3.3percnt;), and apparent distribution volume (0.9 plusmn; 0.4 liters/kg) between fast (n= 4) and slow (n= 5) acetylators, elimination half-life (5.5 plusmn; 1.2 vs 15.3 plusmn; 2.2 hr:p 0.0001), and total plasma clearance (135.3 plusmn; 50.3 vs. 36.9 plusmn; 12.2 ml/min:p= 0.002) demonstrated marked differences between these two phenotypes. In 57 patients with Crohn's disease and 47 patients with ulcerative colitis (53percnt; slow and 47percnt; fast acetylators), plasma levels were monitored routinely. Plasma levels were in the suggested ldquo;therapeuticrdquo; range of 20ndash;50 mu;g total SP/ml in 60percnt; of patients, which was associated in 53percnt; of the cases with a good therapeutic response. Of the 40percnt; of patients exhibiting plasma levels below 20 mu;g/ml, only 27percnt; demonstrated a good response. This difference is probably due to the better absorption seen in well-controlled patients. Multiple plasma level determinations over 0.5ndash;2 years were performed in 9 patients with Morbus Crohn and 2 patients with ulcerative colitis. No significant correlation between dose and plasma levels of SP or its acetylated metabolite was found. In addition, neither SP nor total SP plasma levels demonstrated a relationship with the therapeutic response to sulfasalazine. Thus the existence of a so-called ldquo;therapeuticrdquo; range appears to be highly questionable. Side effects (nausea, headache, vomiting, allergic reactions) were seen with an overall frequency of 17percnt;. In some cases they were associated with high plasma levels.