Affordable Access

deepdyve-link
Publisher Website

Human blood concentrations of cotinine, a biomonitoring marker for tobacco smoke, extrapolated from nicotine metabolism in rats and humans and physiologically based pharmacokinetic modeling.

Authors
  • Yamazaki, Hiroshi1
  • Horiuchi, Kana
  • Takano, Ryohji
  • Nagano, Taku
  • Shimizu, Makiko
  • Kitajima, Masato
  • Murayama, Norie
  • Shono, Fumiaki
  • 1 Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawa Gakuen, Machida, Tokyo 194-8543, Japan. [email protected] , (Japan)
Type
Published Article
Journal
International Journal of Environmental Research and Public Health
Publisher
MDPI AG
Publication Date
Sep 01, 2010
Volume
7
Issue
9
Pages
3406–3421
Identifiers
DOI: 10.3390/ijerph7093406
PMID: 20948932
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The present study defined a simplified physiologically based pharmacokinetic (PBPK) model for nicotine and its primary metabolite cotinine in humans, based on metabolic parameters determined in vitro using relevant liver microsomes, coefficients derived in silico, physiological parameters derived from the literature, and an established rat PBPK model. The model consists of an absorption compartment, a metabolizing compartment, and a central compartment for nicotine and three equivalent compartments for cotinine. Evaluation of a rat model was performed by making comparisons with predicted concentrations in blood and in vivo experimental pharmacokinetic values obtained from rats after oral treatment with nicotine (1.0 mg/kg, a no-observed-adverseeffect level) for 14 days. Elimination rates of nicotine in vitro were established from data from rat liver microsomes and from human pooled liver microsomes. Human biomonitoring data (17 ng nicotine and 150 ng cotinine per mL plasma 1 h after smoking) from pooled five male Japanese smokers (daily intake of 43 mg nicotine by smoking) revealed that these blood concentrations could be calculated using a human PBPK model. These results indicate that a simplified PBPK model for nicotine/cotinine is useful for a forward dosimetry approach in humans and for estimating blood concentrations of other related compounds resulting from exposure to low chemical doses.

Report this publication

Statistics

Seen <100 times