Application of a colon delivery capsule to 5-aminosalicylic acid and evaluation of the pharmacokinetic profile after oral administration to beagle dogs.
Pressure-controlled colon delivery capsule (PCC) containing 5-aminosalicylic acid (5-ASA) for the treatment of inflammatory bowel disease (IBD) was prepared and evaluated by an in vivo experiment using beagle dogs. As a reference drug, sulfasalazine (SASP), prodrug of 5-ASA, was used as a plain gelatin capsule preparation. After the oral administration of SASP at the does of 25.0 mg/kg, the mean time when the plasma 5-ASA concentration reaches to its maximum (Tmax) was 9.0 hr. In the case of 5-ASA administered in PCC, at the doses of 12.5 and 25.0 mg/kg, Tmaxs were 5.3 and 5.3 hr, respectively. Although the time for the first appearance of 5-ASA into the systemic circulation was almost the same value between SASP capsule and PCC containing 5-ASA, longer Tmax was observed from SASP capsule than from PCC. These results suggest that this 5-ASA preparation would be an useful dosage form for the therapy of IBD from the point of avoiding the side effect of sulfapyridine, one of the metabolites of SASP.
Takaya
T
T
Department of Pharmaceutics and Pharmacokinetics, Kyoto Pharmaceutical University, Japan.
Sawada
K
K
Suzuki
H
H
Funaoka
A
A
Matsuda
K
K
Takada
K
K
D000284:Administration, Oral; D000636:Aminosalicylic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002214:Capsules; D003106:Colon / Q000378:metabolism*; D004285:Dogs; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D008297:Male; D019804:Mesalamine
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D019804:Mesalamine