Hepatic uptake of octreotide, a long-acting somatostatin analogue, via a bile acid transport system

Pharm Res. 1995 Jan;12(1):12-7. doi: 10.1023/a:1016222217067.


The hepatic transport mechanism of octreotide (Sandostatin), a somatostatin analogue, was studied using freshly prepared rat hepatocytes. The initial uptake rate of octreotide represented exclusively a saturable transport process. The half-saturation constant, Kt, and the maximum uptake-rate, Jmax, for the uptake of octreotide were 91.1 +/- 28.4 microM and 104.6 +/- 19.7 pmol/mg protein/min, respectively. An energy requirement was demonstrated for [14C]octreotide uptake since metabolic inhibitors (DNP, rotenone, antimycin and NaCN) significantly reduced the initial uptake rate. [14C]octreotide uptake was also significantly inhibited by ouabain. [14C]octreotide uptake was reduced in the absence of Na+ in the uptake medium. [14C]octreotide uptake was significantly inhibited by bile acids, iodipamide, d-tubocurarine, whereas it was not inhibited by bilirubin, TEMA and insulin. Competitive inhibition of taurocholic acid was observed for octreotide uptake with the inhibition constant, Ki, of 82 +/- 17 microM. Moreover, a significant inhibitory effect of octreotide was observed for the Na+ dependent uptake of [14C]taurocholic acid. These results suggest that octreotide is transported into hepatocytes via a bile acid carrier-mediated system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bile Acids and Salts / metabolism*
  • Binding, Competitive
  • Biological Transport
  • Carbon Radioisotopes
  • Cells, Cultured
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Molecular Sequence Data
  • Octreotide / pharmacokinetics*
  • Rats
  • Rats, Wistar
  • Sodium / pharmacology
  • Taurocholic Acid / pharmacology
  • Time Factors


  • Bile Acids and Salts
  • Carbon Radioisotopes
  • Taurocholic Acid
  • Sodium
  • Octreotide