Identification of OATP1B3 as a high-affinity hepatocellular transporter of paclitaxel

Cancer Biol Ther. 2005 Aug;4(8):815-8. doi: 10.4161/cbt.4.8.1867.


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 < 0.0001). OATP1B3-mediated paclitaxel transport was saturable (Michaelis-Menten constant, 6.79 microM), time-dependent, and highly sensitive to chemical inhibition. Paclitaxel uptake was not inhibited by ketoconazole or tariquidar. However, uptake was inhibited by the formulation excipient Cremophor (74.4% inhibition, p < 0.0001), cyclosporin A (25.2%, p = 0.005), glycyrrhizic acid (24.6%, p = 0.012), and hyperforin (28.4%, p = 0.003). Consistent with this finding, Cremophor was found to significantly affect the hepatic uptake of paclitaxel in mice. These data suggest that OATP1B3 is a key regulator of hepatic uptake, and may therefore play a role in the variable response to treatment with taxanes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / metabolism*
  • Female
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Ketoconazole / pharmacology
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism*
  • Liver-Specific Organic Anion Transporter 1
  • Mice
  • Mice, Inbred Strains
  • Oocytes / metabolism
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / physiology
  • Organic Anion Transporters, Sodium-Independent / antagonists & inhibitors
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Organic Anion Transporters, Sodium-Independent / physiology*
  • Paclitaxel / metabolism*
  • Quinolines / pharmacology
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Xenopus laevis


  • Antineoplastic Agents, Phytogenic
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • Organic Anion Transporters, Sodium-Independent
  • Quinolines
  • SLCO1B1 protein, human
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • tariquidar
  • Paclitaxel
  • Ketoconazole