Basic studies on 5-(7-hydroxy-3-O-phosphonocholyl)aminosalicylic acid for the evaluation of microbial overgrowth.
A newly synthesized conjugate of 7-hydroxy-3-O-phosphonocholic acid (ursodeoxycholic acid monophosphate) with 5-aminosalicylic acid (5-ASA-UDCA monophosphate) was investigated to determine its suitability for the evaluation of enteric bacteria. This compound, 5-ASA-UDCA monophosphate, was efficiently deconjugated by cholylglycine hydrolase to release 5-ASA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In everted gut sac experiments, 5-ASA-UDCA monophosphate was not actively absorbed from any part of the small intestine. In animal experiments, urinary excretions of N-acetyl-5-ASA (Ac-5ASA) were measured for 24 h following the oral administration of 20 mg of 5-ASA-UDCA monophosphate. Control rats excreted 276.3 +/- 89.0 micrograms (mean +/- S.E.) of Ac-5ASA, whereas the rats with intestinal bacterial overgrowth excreted more (1224.1 +/- 231.5 micrograms; p < 0.01). These basic studies indicate that this compound is likely to offer a simple method for the evaluation of microbial overgrowth without the use of radioisotopes or expensive, special apparatus.
Konishi
T
T
Department of Hospital Pharmacy, Chugoku Rosai Hospital, Hiroshima, Japan.
Takahashi
M
M
Ohta
S
S
D000636:Aminosalicylic Acids / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D001419:Bacteria / Q000254:growth & development*; D001646:Bile / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D008099:Liver / Q000201:enzymology; D008297:Male; D010194:Pancreatin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics
C106406:5-(7-hydroxy-3-O-phosphonocholyl)aminosalicylic acid; D000636:Aminosalicylic Acids; D014580:Ursodeoxycholic Acid; D010194:Pancreatin