Related Experiment Video

Updated: Jun 13, 2026

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
08:38

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Published on: November 8, 2015

Intracellular concentrations of posaconazole in different compartments of peripheral blood

Fedja Farowski1, Oliver A Cornely, Jörg J Vehreschild

  • 1Klinikum der Universität zu Köln, Klinik I für Innere Medizin, Klinisches Studienzentrum 2 für Infektiologie, Fedja Farowski, MSc, 50924 Cologne, Germany. Fedja.Farowski@ctuc.de

Antimicrobial Agents and Chemotherapy
|May 12, 2010
PubMed

Insights

Therapeutic drug monitoring of antifungal drug concentrations is vital. This study found high intracellular posaconazole concentrations in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes (PMNs), suggesting a role in efficacy.

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Infectious Diseases

Background:

  • Therapeutic drug monitoring (TDM) of antifungal plasma concentrations is increasingly recommended.
  • Limited data exists on antifungal drug concentrations within peripheral blood cell compartments.
  • Understanding drug distribution in different blood cells is crucial for optimizing antifungal therapy.

Purpose of the Study:

  • To quantify intracellular concentrations of posaconazole in various peripheral blood cell types.
  • To compare intracellular and extracellular posaconazole concentrations.
  • To assess the distribution of posaconazole within human blood cells.

Main Methods:

  • Collected 23 blood samples from 14 patients receiving posaconazole for fungal infection prophylaxis.
  • Separated blood samples using Ficoll-Hypaque density gradient centrifugation.
  • Determined intracellular posaconazole concentrations in PBMCs, PMNs, and RBCs using liquid chromatography-tandem mass spectrometry.

Main Results:

  • Intracellular posaconazole concentrations in PBMCs and PMNs were significantly higher than extracellular levels (P < 0.001).
  • Concentration-to-extracellular concentration (C/E) ratios were 22.5 for PBMCs, 7.66 for PMNs, and 0.09 for RBCs.
  • Posaconazole achieved high intracellular concentrations in PBMCs and PMNs, with lower levels in RBCs.

Conclusions:

  • Posaconazole distributes effectively into human PBMCs and PMNs.
  • High intracellular concentrations may contribute to the efficacy and distribution of posaconazole.
  • Further research into intracellular drug levels could refine antifungal TDM strategies.

More Related Videos

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses11:17

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

Demystifying In Vivo Bioluminescence Imaging of a Chagas Disease Mouse Model for Drug Efficacy Studies07:59

Demystifying In Vivo Bioluminescence Imaging of a Chagas Disease Mouse Model for Drug Efficacy Studies

Published on: May 31, 2024

Related Concept Videos

Drug Concentrations: Measurements01:23

Drug Concentrations: Measurements

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 —...
Compartment Models: Two-Compartment Model01:20

Compartment Models: Two-Compartment Model

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...
Drug Distribution: Tissue Binding01:21

Drug Distribution: Tissue Binding

Upon entering the systemic circulation, drugs can distribute into the interstitial and intracellular fluid of various tissue cells. This distribution is facilitated by the binding of drugs to different cellular components within tissues, which may lead to drug accumulation in specific areas. Drugs bound to tissue components serve as reservoirs that release free drugs back into the system, prolonging the drug's overall action. However, this accumulation can also result in local toxicity.
For...
Drug Distribution: Plasma Protein Binding01:29

Drug Distribution: Plasma Protein Binding

Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
Drug Concentration Versus Time Correlation01:15

Drug Concentration Versus Time Correlation

The plasma drug concentration-time curve is a crucial tool in pharmacokinetics, representing the drug's concentration in plasma at different time intervals post-administration. This curve illustrates the drug's journey from absorption into the systemic circulation, distribution to body tissues, and eventual elimination through excretion or biotransformation.
Two pivotal parameters are the minimum effective concentration (MEC) and the minimum toxic concentration (MTC). The MEC is the lowest drug...
Pharmacokinetics in Pediatric Patients: Drug Distribution01:17

Pharmacokinetics in Pediatric Patients: Drug Distribution

Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight, compared...