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Related Concept Videos

Drug Concentrations: Measurements01:23

Drug Concentrations: Measurements

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Drug concentration is the quantity of a drug present in a biological sample. Measuring drug amounts in biological samples allows the clinician to understand how a drug is absorbed, distributed, metabolized, and excreted. Samples can be obtained through invasive or non-invasive methods. Invasive techniques involve surgical or parenteral interventions to gather blood, cerebrospinal fluid, or tissue biopsy. Conversely, non-invasive approaches provide samples like urine, feces, and saliva.
Plasma...
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Bioavailability refers to the proportion of an unaltered drug that, after administration, enters the systemic circulation and can be distributed to the desired action site. Factors such as gastrointestinal (GI) absorption and liver biotransformation influence the bioavailability of a drug when it is administered orally. When a drug is administered intravenously, it enters the systemic circulation directly; by definition, its bioavailability is assumed to be 100%. The bioavailability of an...
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Methods for Studying Drug Absorption: In vitro01:16

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In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
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Methods for Studying Drug Absorption: In situ01:09

Methods for Studying Drug Absorption: In situ

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In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
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Time Course of Drug Effect01:14

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The progression of a drug's impact can be analyzed by examining both the concentration-time course and the effect-time course. The concentration-time course is determined by the drug's half-life and is influenced by factors such as its pharmacokinetics, including absorption, distribution, metabolism, and elimination. The effect of the drug is often related to its concentration in the plasma and is calculated using the maximum drug effect and the plasma concentration that generates 50...
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Compartment Models: Two-Compartment Model01:20

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The two-compartment model divides the body into central and peripheral compartments to account for varying blood perfusion rates among organs and tissues, affecting drug distribution. The central compartment includes blood and highly perfused tissues with rapid drug distribution, while the peripheral compartment contains tissues with slower drug distribution. After a single IV bolus dose, the drug concentration is high in plasma and low in tissues. The drug distribution between compartments...
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  11. The Active Metabolite Hydroxyitraconazole Has Substantially Higher In Vivo Free Fraction And Free Concentrations Compared To Itraconazole

The active metabolite hydroxyitraconazole has substantially higher in vivo free fraction and free concentrations compared to itraconazole

Motoshi Iwao1, Ryota Tanaka1, Yosuke Suzuki2

  • 1Department of Clinical Pharmacy, Oita University Hospital, Yufu, Oita, Japan.

Journal of Pharmaceutical and Biomedical Analysis
|February 28, 2025

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Identification of Small Molecule-binding Proteins in a Native Cellular Environment by Live-cell Photoaffinity Labeling
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Reduced Itraconazole Concentration and Durations Are Successful in Treating Batrachochytrium dendrobatidis Infection in Amphibians
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Reduced Itraconazole Concentration and Durations Are Successful in Treating Batrachochytrium dendrobatidis Infection in Amphibians

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View abstract on PubMed

Summary
This summary is machine-generated.

Hydroxyitraconazole (OH-ITCZ), a major metabolite of itraconazole (ITCZ), has higher free plasma concentrations and a greater free fraction than ITCZ. This suggests OH-ITCZ may be more important for antifungal efficacy, warranting its monitoring.

Area of Science:

  • Pharmacology
  • Analytical Chemistry
  • Clinical Pharmacy

Background:

  • Itraconazole (ITCZ) is a triazole antifungal agent.
  • Hydroxyitraconazole (OH-ITCZ) is the primary active metabolite of ITCZ.
  • Free drug concentration is a superior biomarker for pharmacodynamics compared to total drug concentration.

Purpose of the Study:

  • To develop and validate a sensitive assay for quantifying free ITCZ and free OH-ITCZ.
  • To measure and compare in vivo free concentrations and free fractions of ITCZ and OH-ITCZ in patients.
  • To evaluate the potential contribution of OH-ITCZ to the overall antifungal activity.

Main Methods:

  • Development of an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay.
  • Utilized equilibrium dialysis for separating free drug from protein-bound drug.
Keywords:
Active metaboliteHydroxyitraconazoleIn vivo free concentrationItraconazole

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  • Assay validation according to US Food and Drug Administration guidelines.
  • Measurement of free ITCZ and OH-ITCZ in plasma samples from 11 adult patients.

    • Main Results:

    • The validated assay achieved lower limits of quantification (0.025 ng/mL for free ITCZ, 0.25 ng/mL for free OH-ITCZ).
    • Average plasma free concentrations were 0.188 ng/mL for ITCZ and 1.449 ng/mL for OH-ITCZ.
    • Average percent free fractions were 0.024% for ITCZ and 0.251% for OH-ITCZ.
    • OH-ITCZ exhibited an 8.52-fold higher free fraction and a 10.42-fold higher free concentration than ITCZ.

    Conclusions:

    • OH-ITCZ has significantly higher free plasma concentrations and a greater free fraction compared to ITCZ.
    • Given similar in vitro antifungal activity, OH-ITCZ likely contributes more to in vivo efficacy.
    • Monitoring free OH-ITCZ concentrations may be more beneficial for optimizing antifungal therapy.
    Mass spectrometry