Toxicokinetic analyses of naphthalene, fluorene, phenanthrene, and pyrene in humans after single oral administration.

Sci Total Environ

Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea; Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea. Electronic address:

Published: April 2023

Polycyclic aromatic hydrocarbons (PAHs) are generated by incomplete combustion of organic matter. They have health effects in multiple organs and can cause lung, skin, and bladder cancers in humans. Although data regarding their toxicity is available, information on the absorption, distribution, metabolism, and excretion of PAHs in humans is very limited. In the present study, deuterium-labeled naphthalene (Nap), fluorene (Flu), phenanthrene (Phe), and pyrene (Pyr) were orally administered as a single dose (0.02-0.04 mg/kg) to eight healthy adults. Both serum and urine samples were monitored for 72 h after the exposure. Parent compounds and PAH metabolites (monohydroxy-PAHs; OH-PAHs) were measured by headspace-solid phase microextraction coupled with gas chromatography-mass spectrometry and high-performance liquid chromatography-tandem mass spectrometry, respectively. Based on the time-concentration profiles in serum and urine, non-compartmental analysis was performed, and two-compartment models were constructed and validated for each PAH. Subsequently, all of the parent compounds were rapidly absorbed (T: 0.25 to 1.50 h) after oral administration and excreted in urine with a biological half-life (T) of 1.01 to 2.99 h. The fractional urinary excretion (F) of OH-PAHs ranged from 0.07 % to 11.3 %; their T values ranged from 3.4 to 11.0 h. The two-compartment models successfully described the toxicokinetic characteristics of each PAH and its metabolites. F and the two-compartment models could be useful tools for exposure simulation or dose-reconstruction of PAHs. The results of this study will provide useful information for interpreting biomonitoring data of PAHs.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2023.161899DOI Listing

Publication Analysis

Top Keywords

two-compartment models
12
oral administration
8
serum urine
8
parent compounds
8
pah metabolites
8
toxicokinetic analyses
4
analyses naphthalene
4
naphthalene fluorene
4
fluorene phenanthrene
4
phenanthrene pyrene
4

Similar Publications

Targeted Polymersomes Enable Enhanced Delivery to Peripheral Nerves Post-Injury.

Bioconjug Chem

March 2025

Department of Chemical and Biomolecular Engineering, Clemson University, Clemson, South Carolina 29634, United States.

The gold standard therapy for peripheral nerve injuries involves surgical repair, which is invasive and leads to major variations in therapeutic outcomes. Because of this, smaller injuries often go untreated. However, alternative, noninvasive routes of administration are currently unviable due to the presence of the blood-nerve barrier (BNB), which prevents passage of small molecules from the blood into the endoneurium and the nerve.

View Article and Find Full Text PDF

Proper handling of data below the lower limit of quantification (BLQ) is crucial for accurate pharmacokinetic parameter estimation. The M3 method proposed by Beal uses a likelihood-based approach that is precise but has been reported to suffer from numerical issues in converging. Common alternatives include ignoring the BLQs (M1), imputing half of the lower limit of quantification and ignoring trailing BLQs (M6) or imputing zero (M7).

View Article and Find Full Text PDF

Hereditary angioedema (HAE) is a rare genetic disease that manifests as recurrent, unpredictable, and potentially life-threatening attacks of angioedema. Garadacimab is a first-in-class, fully human, monoclonal antibody targeting activated factor XII (FXIIa) that is under clinical development for the long-term prophylaxis of HAE attacks. We developed population pharmacokinetic (PK)/pharmacodynamic (PD)/exposure-response (ER) models using pooled data across clinical studies to quantify the relationship between garadacimab concentration and the relative risk of HAE attacks and to support the rationale for 200 mg once-monthly dosing.

View Article and Find Full Text PDF

Objective: The aim of this study is to establish a population pharmacokinetic (PK) model for patients undergoing continuous veno-venous hemodiafiltration (CVVHDF) and optimize the dosing regimen of colistin sulfate.

Methods: A prospective observational study in a single center was conducted on patients who were administrated with colistin sulfate and CVVHDF for at least 48 h. Blood samples were obtained prior to dosing and four to six blood samples (primarily C, C, C, C, and C) after dosing.

View Article and Find Full Text PDF

Introduction: The establishment of clinical breakpoints for antimicrobial drug is crucial for guiding appropriate therapeutic interventions. This study aims to identify the pharmacokinetic/pharmacodynamic (PK/PD) cut-offs for using sitafloxacin against target pathogens to support clinical breakpoint establishment for antimicrobial drug sensitivity testing.

Methods: A population PK (PopPK) model was built (342 subjects) to calculate the dosing-regimen-dependent (50 mg q12 h, 100 mg q24 h and 100 mg q12 h) PK parameters of sitafloxacin-infected patients, which were combined with PD data and PK/PD target data.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!