Related Experiment Video
Updated: Nov 12, 2025
High Throughput, Real-time, Dual-readout Testing of Intracellular Antimicrobial Activity and Eukaryotic Cell Cytotoxicity
Published on: November 16, 2016
Which Analysis Approach Is Adequate to Leverage Clinical Microdialysis Data? A Quantitative Comparison to Investigate
David Busse1,2, André Schaeftlein3, Alexander Solms4,5
1Institute of Pharmacy, Department of Clinical Pharmacy and Biochemistry, Freie Universitaet Berlin, Berlin, Germany.
Purpose:
Systematic comparison of analysis methods of clinical microdialysis data for impact on target-site drug exposure and response.
Methods:
39 individuals received a 500 mg levofloxacin short-term infusion followed by 24-h dense sampling in plasma and microdialysate collection in interstitial space fluid (ISF). ISF concentrations were leveraged using non-compartmental (NCA) and compartmental analysis (CA) via (ii) relative recovery correction at midpoint of the collection interval (midpoint-NCA, midpoint-CA) and (ii) dialysate-based integrals of time (integral-CA). Exposure and adequacy of community-acquired pneumonia (CAP) therapy via pharmacokinetic/pharmacodynamic target-attainment (PTA) analysis were compared between approaches.
Results:
Individual AUCISF estimates strongly varied for midpoint-NCA and midpoint-CA (≥52.3%CV) versus integral-CA (≤32.9%CV) owing to separation of variability in PK parameters (midpoint-CA = 46.5%-143%CVPK, integral-CA = 26.4%-72.6%CVPK) from recovery-related variability only in integral-CA (41.0%-50.3%CVrecovery). This also led to increased variability of AUCplasma for midpoint-CA (56.0%CV) versus midpoint-NCA and integral-CA (≤33.0%CV), and inaccuracy of predictive model performance of midpoint-CA in plasma (visual predictive check). PTA analysis translated into 33% of evaluated patient cases being at risk of incorrectly rejecting recommended dosing regimens at CAP-related epidemiological cut-off values.
Conclusions:
Integral-CA proved most appropriate to characterise clinical pharmacokinetics- and microdialysis-related variability. Employing this knowledge will improve the understanding of drug target-site PK for therapeutic decision-making.
More Related Videos
09:58Spatial Quantification of Drugs in Pulmonary Tuberculosis Lesions by Laser Capture Microdissection Liquid Chromatography Mass Spectrometry LCM-LC/MS
Published on: April 18, 2018
11:17Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Related Concept Videos
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
01:20Measurement of Bioavailability: Pharmacodynamic Methods
01:12Analysis of Population Pharmacokinetic Data
01:08Renal Drug Clearance: Comparison Between Renal Excretion Methods
Renal clearance is often associated with the renal glomerular filtration rate (GFR), which represents the rate at which plasma is filtered through the glomeruli in the kidney. When drug reabsorption is minimal and there is no active secretion, renal clearance is closely related to the...
01:30Measurement of Bioavailability: Pharmacokinetic Methods
00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...