Abstract
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 µM 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 µM. 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.
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Terasaki, T., Mizuguchi, H., Itoho, C. et al. Hepatic Uptake of Octreotide, a Long-Acting Somatostatin Analogue, via a Bile Acid Transport System. Pharm Res 12, 12–17 (1995). https://doi.org/10.1023/A:1016222217067
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DOI: https://doi.org/10.1023/A:1016222217067