Salivary excretion and pharmacokinetics of sulfapyridine after sulfasalazine.
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.
Salivary excretion and pharmacokinetics of sulfapyridine after sulfasalazine. 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.