Pharmacokinetics of sulfasalazine metabolites in rats following concomitant oral administration of riboflavin.
Sulfasalazine, 60 mg/kg, was administered orally to groups of rats (n = 4) along with 1, 5, or 10 mg/kg of riboflavin. Plasma and urine were assayed for 5-aminosalicylic acid, acetyl-5-aminosalicylic acid, sulfapyridine, and acetyl-sulfapyridine using an HPLC method. The mean percent of dose recovered as total metabolites in urine was significantly greater (alpha = 0.01) for the group receiving 10 mg/kg riboflavin compared to the controls or the group receiving 1 mg/kg riboflavin. Plasma AUC and Cmax values were also significantly greater (alpha = 0.05) for the 10 mg/kg riboflavin group. These results suggest that at higher doses, a significant fraction of riboflavin reaches the colon intact and stimulates more efficient reduction of the azo bond in sulfasalazine. Since the concentrations of 5-ASA achieved in the colon may be directly related to the efficacy of sulfasalazine in treating inflammatory bowel disease, concomitant administration of riboflavin may enhance sulfasalazine's efficacy in humans.
Chungi
V S
VS
Massachusetts College of Pharmacy and Allied Health Sciences, Boston 02115.
Dittert
L W
LW
Shargel
L
L
D000284:Administration, Oral; D000636:Aminosalicylic Acids / Q000652:urine; D000818:Animals; D004347:Drug Interactions; D006207:Half-Life; D008297:Male; D019804:Mesalamine; D051381:Rats; D012256:Riboflavin / Q000008:administration & dosage / Q000494:pharmacology*; D013427:Sulfapyridine / Q000031:analogs & derivatives / Q000652:urine; D012460:Sulfasalazine / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine
D000636:Aminosalicylic Acids; C005377:N-acetylsulfapyridine; D012460:Sulfasalazine; D019804:Mesalamine; C028836:N-acetyl-5-aminosalicylic acid; D012256:Riboflavin; D013427:Sulfapyridine