Related Experiment Video

Updated: Aug 8, 2026

High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity
09:09

High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity

Published on: November 16, 2016

Inhibition of triazolam clearance by macrolide antimicrobial agents: in vitro correlates and dynamic consequences

D J Greenblatt1, L L von Moltke, J S Harmatz

  • 1Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA.

Clinical Pharmacology and Therapeutics
|October 3, 1998
PubMed
Abstract

Insights

Macrolide antibiotics like erythromycin and clarithromycin can significantly reduce the body's clearance of triazolam, potentially increasing its effects. Azithromycin, however, showed no significant interaction with triazolam clearance in this study.

Area of Science:

  • Pharmacology
  • Drug Metabolism
  • Drug Interactions

Background:

  • Macrolide antibiotics can inhibit hepatic drug clearance via cytochrome P4503A (CYP3A) enzymes.
  • Triazolam is extensively metabolized by CYP3A in humans, making it susceptible to drug interactions.
  • Understanding macrolide-triazolam interactions is crucial for patient safety.

Purpose of the Study:

  • To identify macrolides that interact with triazolam metabolism using an in vitro model.
  • To verify the pharmacokinetic and pharmacodynamic consequences of these interactions in a clinical setting.

Main Methods:

  • In vitro incubations of triazolam with human liver microsomes and varying concentrations of troleandomycin, azithromycin, erythromycin, and clarithromycin.
  • A randomized, double-blind, placebo-controlled clinical study involving 12 volunteers receiving triazolam with placebo or one of three macrolides.

Main Results:

  • In vitro: Troleandomycin, erythromycin, and clarithromycin inhibited 4-hydroxytriazolam formation, while azithromycin did not.
  • In vivo: Erythromycin and clarithromycin significantly reduced triazolam oral clearance, increased peak plasma concentrations, and prolonged elimination half-life.
  • Azithromycin did not alter triazolam pharmacokinetics or pharmacodynamics compared to placebo.

Conclusions:

  • The in vitro metabolic model effectively predicts macrolide-drug interactions involving CYP3A substrates.
  • Erythromycin and clarithromycin are likely to interact with triazolam, necessitating caution in co-administration.
  • Azithromycin appears to be a safer alternative when co-administration with triazolam is necessary.

More Related Videos

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis09:57

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

Published on: April 5, 2017

Assay Development for High-Throughput Drug Screening Against Mycobacteria07:50

Assay Development for High-Throughput Drug Screening Against Mycobacteria

Published on: October 25, 2024

Related Concept Videos

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance01:23

Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance

The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
Therapeutic Drug Monitoring: Affecting Factors01:29

Therapeutic Drug Monitoring: Affecting Factors

Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
Pharmacokinetics: Drug–Drug Interactions01:25

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...
Pharmacodynamic Models: Overview01:27

Pharmacodynamic Models: Overview

Pharmacodynamic (PD) responses describe the interaction between a drug and its biological target, culminating in a physiological effect. These responses can be classified into different types: continuous variables, such as blood glucose levels; categorical outcomes, like survival rates; and time-to-event metrics, such as disease progression. Understanding and modeling PD responses are critical for optimizing drug efficacy and safety.PD models describe the relationship between drug concentration...
Antimicrobial Effectiveness01:28

Antimicrobial Effectiveness

The effectiveness of antimicrobial agents depends on various factors influencing their ability to eliminate microbial populations. Larger microbial populations require more time for complete eradication, emphasizing the importance of population size analysis when evaluating antimicrobial efficacy.Microbial resistance to antimicrobial agents varies significantly. Highly resilient microorganisms include endospores, gram-negative bacteria, and non-enveloped viruses, while prions are exceptionally...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...