Hepatic Uptake of Octreotide,a Long-Acting Somatostatin Analogue,via a Bile Acid Transport System

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, K_t, and the maximum uptake-rate, J_max, 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, K_i, 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.