Salivary excretion and pharmacokinetics of sulfapyridine after sulfasalazine

Abstract

The concentrations of sulfapyridine (SP) and N4-acetylsulfapyridine (AcSP) in the plasma and saliva of 5 healthy male adults (3 slow and 2 rapid acetylators) were determined as a function of time after a single 2.0-gm oral dose of sulfasalazine (salicylazosulfapyridine). SP absorption commenced 3.5 to 6 hr after sulfasalazine administration and occurred slowly (apparent absorption t1/2s ranged from 1.6 to 5 hr) irrespective of acetylator phenotype. Appreciable differences existed between slow and rapid acetylators with respect to the biologic t1/2 and total body clearance of SP. SP concentrations in the saliva correlated well with those in the plasma. The saliva:plasma concentration ratio for SP was 0.559 +/- 0.027 (mean of 5 subjects +/- SE) and was dependent of plasma concentration and saliva pH. The mean saliva:plasma concentration ratio for AcSP was lower (0.246 +/- 0.056), consistent with the pH-partition hypothesis, and showed considerably more intrasubject and intersubject variation than the ratio for SP. These findings suggest that measurement of SP concentrations in the saliva may be a convenient, noninvasive method for monitoring indirectly the steady-state plasma (serum) concentrations of SP in patients with ulcerative colitis or Crohn's disease who are receiving sulfasalazine.

Oro‐caecal transit time in man assessed by the sulfasalazine/sulfapyridine test. Correlation between plasma‐saliva appearance of sulfapyridine

“…The slope of the regression line (0.5 1) represents the ratio of freehotal sufapyridine in plasma. The same ratio was found in previous studies (Bates et al, 1977;Day and Houston, 1980). Only free sulfapyridine diffuses into the saliva, independent of plasma concentration and saliva pH.…”

Azo reduction of sulphasalazine in healthy volunteers.

“…The saliva:plasma concentration ratio for sulphapyridine and its acetyl conjugate has been shown to be constant (Bates et al, 1978;Day & Houston, 1980). Therefore the saliva data presented may be regarded as representative of plasma concentrationtime relationships.…”

“…where AUC and AUC(m) are the areas under the plasma concentration-time curve between zero and infinity for sulphapyridine and its acetyl metabolite, respectively, F and fm are the fractions of the sulphasalazine dose administered (D) (Bates et al, 1978) is not altered by the antibiotic.…”

Saliva: plasma concentration relationships for sulphapyridine following sulphasalazine administration to normal volunteers and patients with inflammatory bowel disease.

“…In a recent publication, Bates, Blumenthal & Pieniaszek (1978) reported saliva :plasma concentration ratios for sulphapyridine and N4-acetylsulphapyridine of 0.56 and 0.25, respectively, following sulphasalazine administration to five healthy volunteers. In this communication we report supporting evidence for the good correlation between sulphapyridine concentrations in saliva and plasma in healthy volunteers, and demonstrate the validity of these relationships in patients with inflammatory bowel disease.…”

“…As shown in (Bates et al, 1978). Therefore the difference in saliva :plasma concentration ratios for SP and ASP cannot be (Fischer & Klotz, 1979) that ASP has a higher affinity than SP for plasma proteins.…”