Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel
NF Smith, MR Acharya, N Desai, W Figg, II… - Cancer biology & …, 2005 - Taylor & Francis
NF Smith, MR Acharya, N Desai, W Figg, II, A Sparreboom
Cancer biology & therapy, 2005•Taylor & FrancisInterindividual variability in paclitaxel and docetaxel pharmacokinetics, toxicity and response
is extensive, and largely unexplained. We hypothesized that this is due to affinity of taxanes
for an uptake transporter that indirectly regulates elimination pathways. Here, we studied
accumulation of [3H] docetaxel and [3H] paclitaxel in Xenopus laevis oocytes injected with
cRNA of the liver-specific organic anion transporting polypeptide (OATP) family members
OATP1B1 (OATP2) or OATP1B3 (OATP8). Taxane transport by OATP1B1 expressing …
is extensive, and largely unexplained. We hypothesized that this is due to affinity of taxanes
for an uptake transporter that indirectly regulates elimination pathways. Here, we studied
accumulation of [3H] docetaxel and [3H] paclitaxel in Xenopus laevis oocytes injected with
cRNA of the liver-specific organic anion transporting polypeptide (OATP) family members
OATP1B1 (OATP2) or OATP1B3 (OATP8). Taxane transport by OATP1B1 expressing …
Interindividual variability in paclitaxel and docetaxel pharmacokinetics, toxicity and response is extensive, and largely unexplained. We hypothesized that this is due to affinity of taxanes for an uptake transporter that indirectly regulates elimination pathways. Here, we studied accumulation of [3H]docetaxel and [3H]paclitaxel in Xenopus laevis oocytes injected with cRNA of the liver-specific organic anion transporting polypeptide (OATP) family members OATP1B1 (OATP2) or OATP1B3 (OATP8). Taxane transport by OATP1B1 expressing oocytes was not significantly different from that by water-injected controls, whereas uptake by OATP1B3 was 2.2-fold higher for docetaxel (P=0.0007) and 3.3-fold higher for paclitaxel (P
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