Pharmacokinetics of trefoil peptides and their stability in gastrointestinal contents.

TY - JOUR

T1 - Pharmacokinetics of trefoil peptides and their stability in gastrointestinal contents.

AU - Kjellev, Stine

AU - Vestergaard, Else Marie

AU - Nexø, Ebba

AU - Thygesen, Peter

AU - Eghøj, Maria S

AU - Jeppesen, Palle B

AU - Thim, Lars

AU - Pedersen, Nis Borbye

AU - Poulsen, Steen Seier

N1 - Keywords: Animals; Area Under Curve; Biological Availability; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Feces; Female; Gastrointestinal Contents; Humans; Injections, Intramuscular; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Mice; Mice, Inbred BALB C; Peptides; Rats; Rats, Wistar; Tissue Distribution

PY - 2007

Y1 - 2007

N2 - Trefoil factor family (TFF) peptides are considered promising for therapeutic use in gastrointestinal diseases, and there is a need to explore the fate of injected TFF and the stability of the peptides in the gastrointestinal tract. We studied the pharmacokinetics of intravenously (i.v.) administered hTFF2 in mice and rats and of hTFF3 administered i.v., intramuscularly, intraperitoneally, and subcutaneously in mice, and estimated by ELISA the decay of the peptides added to rat and human gastrointestinal contents. We found that i.v. injected hTFF2 and hTFF3 were cleared from the circulation within 2-3h, exhibiting comparable pharmacokinetic profiles. In contents from the rat stomach, hTFF levels remained unchanged for up to 6 days. In the small and large intestine of rats, the hTFF levels decreased markedly after 4 and 1h, respectively. In small intestinal contents from humans, the levels remained stable for more than 24h. We conclude that systemically administered hTFF2 and hTFF3 are rapidly eliminated from the circulation and that the stability of hTFF2 and hTFF3 in GI contents appeared higher in the gastric and small intestinal milieu than in the large intestine and feces, suggesting a higher stability toward gastric acid and digestive enzymes than toward microbial degradation.

AB - Trefoil factor family (TFF) peptides are considered promising for therapeutic use in gastrointestinal diseases, and there is a need to explore the fate of injected TFF and the stability of the peptides in the gastrointestinal tract. We studied the pharmacokinetics of intravenously (i.v.) administered hTFF2 in mice and rats and of hTFF3 administered i.v., intramuscularly, intraperitoneally, and subcutaneously in mice, and estimated by ELISA the decay of the peptides added to rat and human gastrointestinal contents. We found that i.v. injected hTFF2 and hTFF3 were cleared from the circulation within 2-3h, exhibiting comparable pharmacokinetic profiles. In contents from the rat stomach, hTFF levels remained unchanged for up to 6 days. In the small and large intestine of rats, the hTFF levels decreased markedly after 4 and 1h, respectively. In small intestinal contents from humans, the levels remained stable for more than 24h. We conclude that systemically administered hTFF2 and hTFF3 are rapidly eliminated from the circulation and that the stability of hTFF2 and hTFF3 in GI contents appeared higher in the gastric and small intestinal milieu than in the large intestine and feces, suggesting a higher stability toward gastric acid and digestive enzymes than toward microbial degradation.

U2 - 10.1016/j.peptides.2007.03.016

DO - 10.1016/j.peptides.2007.03.016

M3 - Journal article

C2 - 17466412

SN - 0196-9781

VL - 28

SP - 1197

EP - 1206

JO - Peptides

JF - Peptides

IS - 6

ER -