title: Evaluation of salmon calcitonin (sCT) enteric-coated capsule for enhanced absorption and GI tolerability in rats.
abstract: BACKGROUND
  Considering the chronic and repeated nature of salmon calcitonin (sCT) therapy, the oral route is a preferred route of administration. But, the oral bioavailability of sCT is very low due to enzymatic degradation and poor permeation across intestinal epithelial cells. It was the aim of this study to investigate the pharmacodynamic (PD), pharmacokinetic (PK), and mucosal injury characteristic of sCT oral delivery system.
  
  
  METHODS
  In this study, PD experiments were performed to find a suitable releasing region of sCT, an effect absorption enhancer, and an optimal mass ratio of sCT/enhancer. In addition, the PK experiments were designed to validate the absorption enhancement of this oral delivery system. Histopathological evaluations on the intestinal mucosa were carried out to assess any potential toxicity of the absorption enhancer.
  
  
  RESULTS
  Through the PD research, we determined that oral sCT enteric-coated capsules containing sCT and citric acid (CA) with a ratio of 1:20 may be an adaptable delivery. PK study further proved that the oral absorption of sCT was enhanced from this delivery system. Finally, no damage on intestinal mucosa was observed when rats received the delivery system containing CA for up to 7 days.
  
  
  CONCLUSIONS
  These results suggested that enteric-coated capsules with a certain amount of CA might give enhanced oral delivery of peptide drugs like sCT.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.forename: Mulan
authors.initials: M
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Zidong
authors.initials: Z
authors.lastname: Gao
authors.forename: Ya
authors.initials: Y
authors.lastname: Sun
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Deen
authors.initials: D
authors.lastname: Han
authors.forename: Xue
authors.initials: X
authors.lastname: Yu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Yaning
authors.initials: Y
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Xijing
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002116:Calcitonin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D019343:Citric Acid; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000009:adverse effects; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D006207:Half-Life; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D050071:Bone Density Conservation Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D019343:Citric Acid; C028815:salmon calcitonin; D002116:Calcitonin; D002118:Calcium