Related Experiment Video
Updated: Dec 14, 2025
05:06
Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
Published on: January 5, 2024
936
Rifampicin Transport by OATP1B1 Variants
Carlijn H C Litjens1,2, Jeroen J M W van den Heuvel2, Frans G M Russel2
1Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands Carlijn.Litjens@radboudumc.nl.
Antimicrobial Agents and Chemotherapy
|July 22, 2020
Summary
Genetic variations in the OATP1B1 transporter affect rifampicin clearance. While OATP1B1 variants *5 and *15 reduce clearance, the clinical impact is likely minor.
Area of Science:
- Pharmacogenomics
- Drug Metabolism
- Molecular Biology
Background:
- Interindividual variability in drug exposure is a significant clinical challenge.
- The organic anion transporting polypeptide 1B1 (OATP1B1) transporter plays a role in the pharmacokinetics of various drugs.
- Single nucleotide polymorphisms (SNPs) in the OATP1B1 gene are associated with altered drug exposure.
Purpose of the Study:
- To investigate the impact of common OATP1B1 genetic variants on rifampicin's intrinsic clearance.
- To quantify the in vitro effect of specific OATP1B1 variants (*1b, *4, *5, *15) on rifampicin transport and metabolism.
Main Methods:
- Utilized HEK293 cells engineered to overexpress wild-type (WT) OATP1B1 and specific variants (*1b, *4, *5, *15).
- Determined the in vitro intrinsic clearance of rifampicin using these engineered cell lines.
- Compared the intrinsic clearance values between WT and variant OATP1B1 transporters.
Main Results:
- OATP1B1 variants *5 and *15 demonstrated a significant reduction in rifampicin intrinsic clearance compared to WT.
- A 36% reduction in intrinsic clearance was observed for OATP1B1*5.
- A 42% reduction in intrinsic clearance was observed for OATP1B1*15.
Conclusions:
- Specific OATP1B1 genetic variants, particularly *5 and *15, can reduce rifampicin's intrinsic clearance.
- Despite observed reductions in vitro, these differences in intrinsic clearance are considered to have minor clinical implications for rifampicin exposure.
- Further clinical studies may be warranted to fully ascertain the impact of these variants on patient outcomes.
Related Concept Videos
01:06Carrier-Mediated Transport
858
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...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
858
01:16Facilitated Diffusion
1000
The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
In this process, substrates such as organic compounds and ions interact with a transporter on one side, triggering conformational changes in proteins that enable...
1000
01:27Nonlinear Pharmacokinetics: Role of Transporters
199
A drug's nonlinear kinetics can be influenced by a diverse range of transporter proteins that serve as crucial players in drug distribution. These transporters, found within cells, can enhance or reduce local drug concentrations by facilitating the influx or efflux of drugs. For instance, the expression of xenobiotic transporters can be influenced by factors such as age and gender, potentially impacting the linearity of drug response.
Polymorphisms occurring in drug transporters can alter...
Polymorphisms occurring in drug transporters can alter...
199
01:44The Significance of Membrane Transport
40.4K
The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
40.4K
01:27ABC Transporters: Importer
3.3K
ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
3.3K
01:17Pore Transport and Ion-Pair Transport
1000
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
1000