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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...

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...

Pharmacokinetics: Drug–Food and Drug–Viral Interactions

Pharmacokinetics: Drug–Food and Drug–Viral Interactions

A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of many...

Therapeutic Drug Monitoring: Affecting Factors

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.

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

Effect of Hepatic Disease on Pharmacokinetics: Active Drug, Metabolite and Fraction of Metabolized Drug

In pharmacotherapy, monitoring drug concentrations is paramount, especially for drugs whose therapeutic effects hinge on both the active compound and its metabolite. Hepatic impairment profoundly influences drug potency by altering liver function. If the drug is more potent than its metabolite, impaired liver function amplifies drug activity due to elevated drug concentration levels. Conversely, if the metabolite holds greater potency, diminished liver function diminishes drug activity by...

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...

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Related Experiment Video

Updated: May 13, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Pharmacokinetic interaction between telaprevir and methadone.

Rolf van Heeswijk¹, Peter Verboven, Ann Vandevoorde

¹Janssen Infectious Diseases BVBA, Beerse, Belgium. rvheesw1@its.jnj.com

Antimicrobial Agents and Chemotherapy

|March 13, 2013

Summary

Hepatitis C virus (HCV) protease inhibitor telaprevir reduced total R-methadone exposure by approximately 30% but did not alter unbound R-methadone levels or cause opioid withdrawal symptoms. Methadone dose adjustment is not required when starting telaprevir.

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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

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Published on: April 9, 2014

Area of Science:

Pharmacology
Hepatology
Infectious Diseases

Background:

Hepatitis C virus (HCV) is prevalent in patients undergoing methadone maintenance therapy.
Interactions between HCV treatments and methadone require investigation to ensure patient safety and treatment efficacy.

Purpose of the Study:

To investigate the pharmacokinetic and safety interactions between the HCV protease inhibitor telaprevir and methadone.
To determine if telaprevir affects methadone exposure and precipitates opioid withdrawal.

Main Methods:

Pharmacokinetic analysis of R- and S-methadone in HCV-negative subjects on stable methadone therapy.
Measurement of unbound R-methadone and assessment of opioid withdrawal symptoms during telaprevir coadministration.
Comparison of methadone pharmacokinetics with and without 7 days of telaprevir (750 mg every 8 hours).

Main Results:

Telaprevir reduced total R-methadone plasma concentrations (Cmin, Cmax, AUC0-24) by approximately 29-31%.
The ratio of S-methadone to R-methadone and the unbound percentage of R-methadone were altered, but absolute unbound R-methadone levels remained similar.
No symptoms of opioid withdrawal or adverse events leading to discontinuation were reported.

Conclusions:

Telaprevir significantly reduces total R-methadone exposure but does not affect unbound R-methadone levels or cause opioid withdrawal.
Methadone dose adjustment is likely unnecessary when initiating telaprevir treatment in patients on stable methadone therapy.
These findings support the coadministration of telaprevir and methadone without altering methadone dosage.