| 7724472 |
Terasaki T, Mizuguchi H, Itoho C, Tamai I, Lemaire M, Tsuji A: Hepatic uptake of octreotide, a long-acting somatostatin analogue, via a bile acid transport system. Pharm Res. 1995 Jan;12(1):12-7.
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. |
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