Related Experiment Video

Updated: Apr 17, 2026

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

14.2K

Contribution of hepatic organic anion-transporting polypeptides to docetaxel uptake and clearance

Hannah H Lee1, Brenda F Leake1, Wendy Teft2

  • 1Division of Hematology and Oncology, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.

Molecular Cancer Therapeutics
|February 20, 2015
PubMed

Insights

This study identifies organic anion-transporting polypeptides (OATP) as key transporters for docetaxel uptake. These OATP transporters significantly influence docetaxel

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Molecular Biology

Background:

  • Docetaxel is a vital chemotherapeutic agent for solid tumors.
  • Hepatic disposition is crucial for docetaxel's efficacy.
  • Understanding docetaxel transport mechanisms is essential for optimizing treatment.

Purpose of the Study:

  • To identify and characterize drug uptake transporters involved in docetaxel transport.
  • To investigate the impact of genetic variations in transporters on docetaxel pharmacokinetics.
  • To elucidate the role of OATP transporters in docetaxel's hepatic disposition and clearance.

Main Methods:

  • Screening of drug uptake transporters in HeLa cells using a recombinant vaccinia-based method.
  • Kinetic analysis of docetaxel transport by identified transporters.
  • Assessment of single nucleotide polymorphisms (SNPs) in SLCO1B1 and SLCO1B3 genes.
  • Vectorial transport assays using MDCKII stable cell lines.
  • In vivo studies in Slco1b2 knockout mice.

Main Results:

  • Five organic anion-transporting polypeptides (OATP1A2, OATP1B1, OATP1B3, OATP1C1, and Oatp1b2) were identified as docetaxel uptake transporters.
  • Hepatic OATP1B/1b transporters exhibited similar kinetic parameters for docetaxel transport.
  • Certain OATP1B1 and OATP1B3 variants, due to SNPs, impaired docetaxel transport.
  • Docetaxel showed significantly higher apical transport in double-transfected MDCKII cells (OATP1B1/MDR1 and OATP1B3/MDR1).
  • Slco1b2(-/-) mice displayed higher plasma docetaxel concentrations, reduced liver-to-plasma ratio, and significantly lower plasma clearance compared to wild-type mice.

Conclusions:

  • OATP1B transporters play a critical role in the hepatic disposition and clearance of docetaxel.
  • These transporters are essential for understanding docetaxel pharmacokinetics.
  • The findings highlight the clinical relevance of OATP transporters in docetaxel therapy and potential for personalized medicine.

More Related Videos

High-Throughput In Vitro Assay using Patient-Derived Tumor Organoids06:25

High-Throughput In Vitro Assay using Patient-Derived Tumor Organoids

Published on: June 14, 2021

6.2K
Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice08:41

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

Published on: October 27, 2014

24.2K

Related Concept Videos

Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
373
Carrier-Mediated Transport01:06

Carrier-Mediated Transport

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
1.6K
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
384
Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
781
Drug Elimination by Renal Route: Tubular Secretion01:15

Drug Elimination by Renal Route: Tubular Secretion

Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
3.8K
Hepatic Drug Clearance: Effect of Protein Binding01:09

Hepatic Drug Clearance: Effect of Protein Binding

Hepatic clearance is influenced by protein binding based on the drug's extraction ratio. Drugs with high extraction ratios are considered flow-limited and remain unaffected by protein binding during hepatic clearance. On the other hand, drugs with low extraction ratios may be impacted by plasma protein binding, although the extent of this influence depends on the fraction of the drug bound.
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
697