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Nonlinear Pharmacokinetics: Role of Transporters

Nonlinear Pharmacokinetics: Role of Transporters

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...

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...

Pharmacogenetics of Drug Metabolism: Overview

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

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, mediated...

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...

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Related Experiment Video

Updated: May 18, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Published on: May 28, 2014

Polymorphic transporters and platinum pharmacodynamics.

Jason A Sprowl¹, Rachel A Ness, Alex Sparreboom

¹Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Drug Metabolism and Pharmacokinetics

|September 19, 2012

Summary

Genetic variations in transporters significantly impact how platinum-based chemotherapy drugs like cisplatin are processed by the body. Understanding these genetic factors is key to managing drug disposition and treatment effectiveness.

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High-Throughput Expression and Purification of Human Solute Carriers for Structural and Biochemical Studies

High-Throughput Expression and Purification of Human Solute Carriers for Structural and Biochemical Studies

Published on: September 29, 2023

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Last Updated: May 18, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Published on: May 28, 2014

Dose Uptake of Platinum- and Ruthenium-based Compound Exposure in Zebrafish by Inductively Coupled Plasma Mass Spectrometry with Broader Applications

Dose Uptake of Platinum- and Ruthenium-based Compound Exposure in Zebrafish by Inductively Coupled Plasma Mass Spectrometry with Broader Applications

Published on: April 21, 2022

High-Throughput Expression and Purification of Human Solute Carriers for Structural and Biochemical Studies

High-Throughput Expression and Purification of Human Solute Carriers for Structural and Biochemical Studies

Published on: September 29, 2023

Area of Science:

Pharmacology and Molecular Biology
Cancer Therapeutics
Genetics and Personalized Medicine

Background:

Platinum-based chemotherapeutic agents (e.g., cisplatin, carboplatin, oxaliplatin) are crucial in cancer treatment.
Significant interindividual variability exists in the pharmacokinetics of these drugs.
Solute carriers (SLCs) and ATP-binding cassette (ABC) transporters are known to influence drug influx and efflux.

Purpose of the Study:

To review the role of various transporters in the cellular transport of platinum-based chemotherapy agents.
To explore the association between transporter genetic status, drug disposition, and pharmacodynamic effects.
To provide an updated overview of transporters implicated in platinum agent pharmacokinetics.

Main Methods:

Literature review of studies involving animal models and human patient populations.
Analysis of research implicating SLCs and ABC transporters in platinum agent transport.
Examination of the link between transporter polymorphism and drug pharmacokinetics/pharmacodynamics.

Main Results:

Multiple SLC and ABC transporters facilitate the movement of platinum-based drugs across cell membranes.
High polymorphism in these transporters suggests a significant contribution to pharmacokinetic variability.
Transporter function is associated with both drug disposition (absorption, distribution, metabolism, excretion) and therapeutic effects.

Conclusions:

Transporter proteins are critical determinants of platinum-based chemotherapy efficacy and toxicity.
Genetic variations in transporters represent a key factor in interindividual pharmacokinetic differences.
Targeting or considering transporter status may lead to more personalized platinum-based cancer therapy.