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Pharmacokinetics: Drug–Drug Interactions

Pharmacokinetics: Drug–Drug Interactions

Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...

Drug toxicity: Drug–Drug Interaction

Drug toxicity: Drug–Drug Interaction

Drug–drug interactions can precipitate toxicity through multiple mechanisms. Absorption interactions alter how drugs enter the body, exemplified when ranitidine increases the absorption of basic drugs, while cholestyramine decreases the levels of propranolol. Protein binding interactions occur when drugs share the same binding sites on plasma proteins. Drugs like aspirin and warfarin, when bound in excess, can lead to increased free drug concentrations, enhancing the potential for...

Carrier-Mediated Transport

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...

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.
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Hepatic Drug Clearance: Role of Transporters

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...

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...

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Related Experiment Video

Updated: Jul 3, 2026

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Published on: October 17, 2013

A regulatory viewpoint on transporter-based drug interactions.

L Zhang¹, Y D Zhang, J M Strong

¹Offices of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.

Xenobiotica; the Fate of Foreign Compounds in Biological Systems

|August 1, 2008

Summary

Drug transporters significantly impact drug absorption, distribution, metabolism, and elimination, influencing drug-drug interactions. Regulatory guidance now emphasizes evaluating transporter roles, particularly P-glycoprotein (P-gp), during drug development.

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Area of Science:

Pharmacology
Drug Development
Regulatory Science

Background:

Pharmacokinetic drug interactions pose risks, necessitating thorough evaluation during drug development.
Drug transporters are increasingly recognized for their role in modulating drug pharmacokinetics and pharmacodynamics.
Recent US Food and Drug Administration (USFDA) guidance highlights drug transporter interactions, focusing on P-glycoprotein (P-gp, ABCB1).

Purpose of the Study:

To provide a regulatory perspective on transporters and their role in drug-drug interactions.
To outline data requirements for new drug applications (NDAs) concerning transporter-mediated interactions.
To detail criteria for conducting in vivo P-gp interaction studies based on in vitro data.

Main Methods:

Review of regulatory guidelines and scientific literature on drug transporters.
Analysis of data submission requirements for new molecular entities (NMEs).
Case study evaluation of P-gp induction interactions.

Main Results:

Transporter-mediated interactions are critical for drug safety and efficacy.
Specific in vitro assessments can guide the need for in vivo studies.
Regulatory submissions must address potential transporter roles in drug-drug interactions.

Conclusions:

Understanding transporter roles is essential for comprehensive drug development and regulatory approval.
P-gp is a key transporter requiring careful evaluation for drug interaction potential.
Proactive assessment of transporter-mediated drug interactions ensures safer drug products.